WO2013012276A2 - Régulateur génique d'une réaction magnétique de l'hydrogène et procédé de régulation génique - Google Patents

Régulateur génique d'une réaction magnétique de l'hydrogène et procédé de régulation génique Download PDF

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Publication number
WO2013012276A2
WO2013012276A2 PCT/KR2012/005790 KR2012005790W WO2013012276A2 WO 2013012276 A2 WO2013012276 A2 WO 2013012276A2 KR 2012005790 W KR2012005790 W KR 2012005790W WO 2013012276 A2 WO2013012276 A2 WO 2013012276A2
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Prior art keywords
electromagnet
magnetic field
driving
electromagnets
base pair
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Korean (ko)
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WO2013012276A3 (fr
Inventor
이석근
김연숙
이윤우
이정근
이홍근
이대성
이대관
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GENE BIOSYS Corp
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GENE BIOSYS Corp
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Priority claimed from KR1020120078812A external-priority patent/KR101513997B1/ko
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Publication of WO2013012276A3 publication Critical patent/WO2013012276A3/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N2/00—Magnetotherapy
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2999/00—Further aspects of viruses or vectors not covered by groups C12N2710/00 - C12N2796/00 or C12N2800/00
    • C12N2999/005—Biological teaching, e.g. a link between protein and disease, new virus causing pandemic

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  • the present invention relates to a hydrophilic response gene regulator and a gene control method, and more particularly, by using a magnetic field generated from a pair of electromagnets arranged in a circular shape, a hydrophobic reaction occurs on a hydrogen bond of a specific DNA double-strand base pair to generate a related gene. It relates to a hydrophobic response gene regulator for activating or deactivating and a method of using the same.
  • 1 is a schematic diagram showing an orbital motion of electrons generated by a magnetic field.
  • FIG. 2 is a schematic representation of the magnetic reaction of hydrogen atoms in a magnetic field that is not too strong, for example a weak magnetic field of 10 3 Gauss or less.
  • the magnetic field can change the orbital movement of the outer electrons in the hydrogen atoms. As a result, the hydrogen bonding force can be changed.
  • Korean Patent Publication No. 0384924 discloses a technique for controlling gene expression by affecting hydrogen bonding by applying a circulating magnetic field.
  • the invention is merely illustrative, and there is a lack of theoretical explanation, which limits the expression of genes.
  • the present invention uses a polar or semi-polar magnetic field generated in the electromagnet array of the circular structure to provide a hydrophobic reaction gene regulator and gene control method to control the gene expression by generating a hydrophobic reaction to the hydrogen bond of the DNA double helix base pair It is for.
  • the hydrophilic reaction gene regulator of the present invention has a polarity in which a polar magnetic field or a semipolar magnetic field corresponding to base pairs of an even number of electromagnets and target DNA double helixes arranged at equal intervals on a virtual circle is generated.
  • the electromagnet pair of the electromagnet may include an electromagnet driver for sequentially driving the base pair of the sense strand or the antisense strand in the base pair of the target DNA double helix.
  • the polar magnetic field is received by the base pair when the pyrimidine series is on the first pole side and the purine series is on the second pole side of the base pair. It is a magnetic field, and the semipolar magnetic field may be a magnetic field received by the base pair when the purine series is located at the first pole side and the pyrimidine series is at the second pole side of the base pair.
  • the driving time of the electromagnet pair may vary depending on the base pair of the target DNA double helix.
  • the driving time of the electromagnet pair is about 10 ⁇ 300msec, and varies depending on the activity of the target DNA, such as bacteria, plants, animals.
  • the ratio of the T (thymine): A (adenine) base pair to the C (cytosine): G (guanine) base pair constituting the target DNA base pair may have a driving time of about 1/2 to 3/4.
  • the driving time of an electromagnet pair may be rapidly progressed to 50 msec or less, and may be relatively slow to about 150 msec or less in an animal and about 300 msec or less in a plant.
  • the magnetic field formed in the center of the virtual circle by the pair of electromagnets may be more than 1T at about 50 ⁇ T (Tesla) of the Earth's magnetic field strength, depending on the purpose of use, the electromagnet drive unit drives only a pair of electromagnets facing at a temporary point You can.
  • the number of electromagnets is the number of base pairs arranged in one rotation section of the target DNA double helix, and may be 8 to 14 according to the shape change of the target DNA.
  • the electromagnet driver may drive the pair of electromagnets from the first base sequence to the last base sequence of the sense strand in a counterclockwise or clockwise direction with a polar magnetic field or a semipolar magnetic field corresponding to the sense strand base sequence, and then Rotate the pair of electromagnets from the first base sequence to the final base sequence of the antisense strand with a polar or semipolar magnetic field corresponding to the antisense strand sequence, starting with the electromagnet pair driven corresponding to the final sequence of the sense strand. It can be driven in the opposite direction.
  • the one-time driving of the target DNA may be performed for 4 to 100 base pairs in the target DNA double helix.
  • the electromagnet driving unit may repeat one drive for the target DNA by a set time.
  • the electromagnet drive unit repeats the one-time drive of the electromagnet pair by using a pair of electromagnets adjacent in the counterclockwise direction from the one-time drive start electromagnet pair after the repetition of the first drive. You can repeat as many times as you like.
  • auxiliary electromagnets are further disposed on both sides of the virtual line orthogonal to the virtual circle center, and the electromagnet driving unit drives the auxiliary electromagnet in a direction orthogonal to an array of electromagnet pairs arranged in a circle between the single drivings. You can.
  • the magnetic field among the electromagnetic fields generated by the pair of electromagnets is concentrated on the center of the circle, whereas most electric fields are radiated outwardly orthogonal to the direction of magnetic field in the coil region of the electromagnets.
  • the interference of the electric field can be minimized by installing an electric field shielding film using a nonmagnetic metal on the circle center.
  • the effect of the electric field is relatively very small in the dehydrogenase response gene regulator of the present invention can be carried out mainly through the effect of the magnetic field (magnetic effect).
  • the apparatus may further include an electromagnetic shielding film for shielding the magnetic field scattered from the electric field generated outside the imaginary circle among the electromagnetic fields generated by the electromagnets, and a cooling device for reducing heat generated by driving the electromagnet.
  • the method for regulating a hydrophilic reaction gene of the present invention is a polarity in which a polar magnetic field or a semipolar magnetic field corresponding to a base pair of a target DNA double helix is generated, and an electromagnet pair facing each other among an even number of electromagnets arranged at equal intervals on a virtual circle.
  • a driving step may be sequentially performed according to the base sequence of the sense strand or antisense strand in the base pair of the target DNA double helix.
  • hydrophilic response gene control method of the present invention can be recorded as a program executed in a computer on a computer readable medium.
  • the apoptotic-responsive gene regulator and gene regulation method of the present invention are a polar magnetic field or a semi-polar magnetic field corresponding to the base pair of the double helix of the target DNA in an even number of electromagnets arranged at equal intervals on the imaginary circle.
  • 1 is a schematic diagram showing an orbital motion of electrons generated by a magnetic field.
  • Figure 2 is a schematic diagram showing the change of the outer electron orbital movement of the hydrogen atom by the magnetic field.
  • Figure 3 is a schematic diagram showing the effect of the weak magnetic field on the hydrogen bond that the hydrogen atom of the hydrogen compound is made with the oxygen atom of the other compound.
  • Figure 4 is a schematic diagram showing the general structure of the hydrophilic response gene regulator of the present invention.
  • Figure 5 is a schematic diagram showing an example of the polar magnetic field driving for the base pair of the DNA double helix in the hydroreceptor gene regulator of the present invention.
  • FIG. 6 is a schematic diagram for explaining a polar magnetic field and a semipolar magnetic field.
  • Figure 7 is a schematic diagram for calculating the maximum efficiency capable of regulating the hydrophilic response gene of the present invention for DNA double helixes present randomly in three-dimensional space.
  • FIG. 8 is a graph showing experimental results of a polar magnetic field for oligo DNA double helix of 6T6A.6T6A and 11C1A.1T11G.
  • Figure 9 is a schematic diagram showing the results of experiments to know that the DNA cleavage function of the restriction enzyme is activated by hydrolysis of the pBluescript SK (-) plasmid DNA with XhoI DNA restriction enzyme.
  • FIG. 10 is a schematic diagram showing a state in which a progesterone-responsive gene regulator is applied to an early carcinoma in which a mass of about 3 mm in diameter is visually observed after implanting a human prostate carcinoma subcutaneously.
  • FIG. 11 shows randomized magnetic field (randome GR), reverse PEMF, and polar magnetic field (PEMF) irradiation groups of medium-term carcinomas grown in nude mice with a diameter of about 1 cm. Schematic diagram showing the results of experiments divided by.
  • FIG. 12 is a schematic diagram showing a state in which a prostate cancer cell (DU-145) is implanted in a shoulder subcutaneous tissue of a nude mouse to apply a hydrophobic response gene regulator to a terminal cancer mass grown to about 2 cm in diameter.
  • a prostate cancer cell DU-145
  • Figure 13 is a flow chart showing a method for controlling the hydrophilic response gene of the present invention.
  • the north pole and the south pole described in the present specification may be regarded as the polarity of the actual magnet.
  • the apoptotic response gene regulator may be abbreviated as a gene regulator.
  • FIG. 2 the polarization of hydrogen atoms in a weak magnetic field environment has been described.
  • a hydrophilic reaction occurring on a hydrogen atom in a weak magnetic field environment may affect related hydrogen bonds.
  • a single spin motion of the outer electrons of a hydrogen atom creates an empty electron hole, creating hydrogen bonds with various atoms such as O, N, F, and S.
  • the energy level of the outer electron orbit of a hydrogen atom is changed by a magnetic field, the corresponding hydrogen atom This will have a direct impact on the hydrogen bonds they form with other atoms.
  • FIG. 3 is a schematic diagram showing the effect of a weak magnetic field on the hydrogen bond that hydrogen atoms of hydrogen compounds form with oxygen atoms of other compounds.
  • the hydrogen bonding force may be increased or decreased due to the Zeman effect even by the polarity change of the weak magnetic field of less than about 1000 Gauss.
  • This change in hydrogen bonding force can be mainly calculated as the change in the spin orbital interaction momentum of the single outer electron of the hydrogen atom.
  • g Lande g factor and B is approximately 50 Gauss as the strength of the magnetic field.
  • ⁇ B is the Bohr magneton, which has a value of 5.788 x 10 -5 eV / T, and m j is the magnitude of the slitting caused by the weak magnetic field of the P 3/2 and P 1/2 states of the outer electrons.
  • the converted E value is about 0.579 ⁇ eV.
  • the above E value (about 0.579 ⁇ eV), although very small, can be amplified by repeated irradiation of the magnetic field if it can be used as an electrostatic charge in hydrogen bonds.
  • the phosphate group is easily activated by the close interaction between the ribose ring and the phosphate group in the DNA nucleic acid structure, the electrostatic charge generated at the hydrogen bond of the base pair may be transferred to and accumulated in the phosphate group.
  • the one-time driving of the E value (0.579 ⁇ eV) is repeatedly accumulated 200 times, it becomes about 120 ⁇ eV, and this force causes the outer electrons to perturb in the orthogonal direction to about 605 ⁇ eV, which is the intrinsic hydrogen bonding force of the DNA base pair, thereby causing the spin precession (
  • the distance between hydrogen bonders can be changed as shown in FIG.
  • the intrinsic hydrogen bonding force of the DNA base pair is about 605 ⁇ eV (a vector) and the converted E ⁇ value (120 ⁇ eV, b vector) are combined to change the distance between the hydrogen bonders with the force of the c vector value (about 617 ⁇ eV).
  • the increase in the hydrogen bonding force between the hydrogen bonds by the magnetic field is in the case of the direction of the magnetic field shown in FIG.
  • the magnetic field is irradiated in a direction parallel to the hydrogen bond, and the hydrogen atom is located on the S pole of the magnetic field.
  • ⁇ is the distance between the hydrogen bonds created by the forces of c and c, which are attracted to each other by the spin-orbit interaction forces b and b ⁇ of the electrons in the direction of pulling each other for the hydrogen bond forces a and a ⁇ . Shorter (a, b, c are from hydrogen atoms, a, b, c are forces from oxygen atoms).
  • the polarization of the hydrogen atoms is greatly caused by the magnetic field, and the distance between the outermost electrons of the hydrogen atoms and the oxygen atoms is near.
  • the hydrogen bonding force is reduced between the hydrogen bonds by the hydrolysis reaction.
  • the magnetic field is irradiated in the parallel direction of the hydrogen bond, and the hydrogen atom is located on the N pole side of the magnetic field.
  • ⁇ is the distance between the hydrogen bonds created by the forces of c and c ⁇ that are pushed together by the spin-orbit interaction forces b and b ⁇ of the electrons in the direction pushing against each other, a and a ⁇ . Longer (a, b, c are from hydrogen atoms, a, b, c are forces from oxygen atoms).
  • the distance between the hydrogen atoms and the outermost electrons of the oxygen atoms is increased by the magnetic field, so that the hydrogen bonding force is weakened, and the hydrogen atoms and oxygen atoms are polarized in opposite directions.
  • DNA double helix is a structure in which complementary sequences of opposite directions located on two DNA single strands are bonded by hydrogen bonds.
  • all nucleic acids are regularly linked as an phosphate ester structure.
  • the phosphate groups of DNA nucleic acids are located outside and the bases are located inside.
  • the bases inside the DNA double helix are hydrophobic in the aqueous solution by the strong hydrophobic pyrimidine ring, the purine ring, and the weakly hydrophobic ribose ring. Midines and purine bases can form stable hydrogen bonds in the center of a DNA double helix.
  • Hydrogen bonds generated between base pairs of DNA double helixes are hybrid states without electron transfer between hydrogen bonders.
  • electrostatic charge tends to increase as the hydrogen bond force increases.
  • the DNA sequence of the base sequence has a characteristic DNA structure that facilitates the binding of a specific transcription factor such as a DNA attachment protein.
  • DNA attachment proteins can be attached to DNA double helix selectively or competitively.
  • the base pair of the target DNA double helix can be activated or deactivated by using a polar magnetic field or a semipolar magnetic field for hydrogen bonding of the DNA base pair. Can effectively control structure and function.
  • DNA duplex segments are formed in DNA double helix due to the electron transport characteristics due to the complementary polarity of the DNA double helix base pair and the DNA base pair polarity in the 5 ⁇ to 3 ⁇ direction on both strands of the DNA double helix. Can be.
  • All DNA double helix codes can be divided into DNA double helix nodes, which accumulate a constant amount of electrostatic charge to form a stable DNA double helix structure and to perform the unique functions of a unique DNA double helix.
  • the electrostatic charge of the DNA double helix base pair generated by the gene regulator of the present invention can be accumulated in the target DNA double helix node to perform a desired gene control function.
  • Figure 4 is a schematic diagram showing the general structure of the hydroresponsive gene regulator of the present invention
  • Figure 5 is a schematic diagram showing a polar magnetic field driving example for the base pair of DNA double helix in the hydrophilic response gene regulator of the present invention.
  • the genetic regulator targets the pair of electromagnets facing each other in the electromagnet with polarities such that a polar magnetic field or a semipolar magnetic field corresponding to the base pair of the target DNA double helix and the even number of electromagnets 110 are arranged at equal intervals on the virtual circle. It includes an electromagnet drive unit 130 to sequentially drive in accordance with the base sequence of the sense strand or antisense strand in the base pair of the DNA double helix.
  • the base forming the base sequence of the target DNA includes a purine series and pyrimidine series.
  • the polar magnetic field has the pyrimidine series at the first pole side and the purine series at the second pole side in the DNA base pair.
  • the base pair receives the magnetic field, and the semipolar magnetic field is the magnetic field received by the base pair when the purine series is on the first pole side and the pyrimidine series is on the second pole side of the DNA base pair.
  • the first pole may be the N pole
  • the second pole may be the S pole
  • vice versa even if the direction of the magnetic field and the direction parallel to the hydrogen bond of the base pair differ in some degrees, for example, the angle difference within 30 degrees, it can be said to correspond to a polar magnetic field or a semipolar magnetic field.
  • the directions of the polar magnetic field or the semipolar magnetic field with respect to the base pair of the DNA double helix have mutually opposite magnetic field directions with respect to the base sequence of the sense strand and the constant base pair of the antisense strand.
  • Electromagnet 110 may be even numbered on the imaginary circle at equal intervals. Accordingly, opposing electromagnets are located on opposite sides of each electromagnet. In other words, assuming a reference circle crossing an imaginary circle center and an arc of the circle, the electromagnet is disposed at two intersection points of the reference line and the arc. At this time, the DNA double helix may be disposed in or near the virtual circle center, and the virtual circle center becomes the main reaction site.
  • DNA double helix is a structure in which complementary sequences of opposite directions located on two DNA single strands are bonded by hydrogen bonds.
  • the base pairs contained in the DNA are arranged in a double helix structure that rotates counterclockwise in both directions, wherein the arrangement direction of each base pair hydrogen bond is almost identical to the horizontal plane orthogonal to the DNA double helix.
  • the arrangement direction of base pairs can be equally spaced from adjacent base pairs as viewed from above, i.e., they have the same or similar angular spacing in plan view.
  • the polar magnetic field is a magnetic field that proceeds in a straight line from the pyrimidine series to the purine series in the DNA base pair
  • the pair of electromagnets facing each other is aligned in a straight line so as to match or approximate the planar angle of the rotating base pair. It must be arranged. For this purpose, an even number of electromagnets may be arranged on the virtual circle at equal intervals.
  • the number of electromagnets may be the number of base pairs arranged in one rotation section of the double helix formed by the target DNA.
  • the number of electromagnets may be 10 when the target DNA is B-type DNA, and 12 when the target DNA is Z-type DNA.
  • About 10.5 base pairs are arranged in one rotation section of the DNA double helix in type B DNA, and about 11.3 base pairs are arranged in one rotation section of the DNA double helix in Z type DNA.
  • the number of base pairs is 10.5, electromagnets cannot be placed in the number of decimal points, so if the decimal point is rounded up, the number is rounded up to 11, but the result is not even. The reason for doing this is that if one electromagnet is added to match an even number, a total of 12 electromagnets are generated.
  • electromagnets are arranged in a circle on the B-type DNA, and twelve electromagnets are arranged in a circle on the Z-type DNA.
  • the number of electromagnets may be six to fourteen. However, even in such a case, the number of electromagnets in the range of 6 to 12 is determined for the B-type DNA, and the number of electromagnets in the range of 10 to 14 is preferably determined for the Z-type DNA.
  • the S pole should be located on the Purine series side of the DNA base pair and the N pole on the pyrimidine series side.
  • two opposing electromagnets must be driven simultaneously with the opposite polarity according to the base pair sequence. This can be accomplished by driving two electromagnets facing each other, that is, electromagnet pairs connected in series or in parallel in the same electromagnet coil polarity direction as shown in FIG. 6.
  • the electromagnet driver 130 drives the electromagnet 110 by selecting a current direction to generate a polar magnetic field or a semipolar magnetic field.
  • each electromagnet pair may be connected in series or parallel in the same electromagnet coil polarity direction in the electromagnet pair facing each other as shown in FIG.
  • each sense strand sequence is sequentially driven by electromagnet numbers 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and each antisense strand sequence is 12, Drive sequentially with, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1.
  • the pairs of electromagnets facing each other, 1-7, 2-8, 3-9, 4-10, 5-11, 6-12 may generate a polar magnetic field or a semipolar magnetic field according to sense or antisense sequences. .
  • the base sequence of the same DNA has two sense strands and an antisense strand.
  • the nucleotide sequence of the sense strand and the antisense strand may be as follows.
  • Antisense Strand 3 '-A G T C G T G C T A C T-5'
  • the DNA double helix twisted in vivo is likely to be about 1-10 turns, so the DNA regulator can target a DNA double helix of about 100 base pairs in size, but in this example, the Z-type DNA double helix is 1
  • the target was a spinning DNA double helix about 12 base pairs in size.
  • DNA double helixes of 12 base pairs match the arrangement of 12 electromagnets, which can be easily described.
  • a magnetic field irradiation method for driving a polar magnetic field for the DNA double helix is shown as follows.
  • the direction in which the electromagnet pairs are sequentially driven may be clockwise or counterclockwise.
  • the electromagnet driving unit drives the electromagnet 1 to the N pole having the first polarity in the electromagnet pair 1-7 arbitrarily selected among electromagnets arranged in a circle.
  • the electromagnet 7 can be driven to the S pole opposite to the electromagnet 1 to drive the polar magnetic field of the T: A base pair.
  • the pair of electromagnets selected arbitrarily and driven for the first time is called a driving start electromagnet pair, and the electromagnet 2 is driven to the second polarity N pole and the electromagnet 8 is driven to the S pole from the electromagnets 2-8 adjacent to the driving start electromagnet pair counterclockwise.
  • the polar magnetic field of the C: G base pair can be driven.
  • the electromagnet 3 -9 adjacent to the electromagnet pair 2-8 in the counterclockwise direction is driven to the S pole which is the third polarity, and the electromagnet 9 is driven to the N pole to drive the polar magnetic field of the A: T base pair. can do.
  • the electromagnet drive unit is equipped with electromagnets 4, 5, 6 in the pairs 4-10, 5-11, 6-12, 7-1, 8-2, 9-3, 10-4, 11-5, and 12-6.
  • 7, 8, 9, 10, 11, 12 are sequentially driven to S, N, S, N, S, S, N, S, S poles.
  • the paired electromagnets 10, 11, 12, 1, 2, 3, 4, 5, and 6 are driven to the opposite polarities N, S, N, S, N, N, S, N and N poles.
  • the following driving method can be used to drive one rotation of the polar magnetic field for a DNA double helix consisting of 12 base sequences as described above using 12 electromagnets arranged uniformly in a circle.
  • the electromagnet driving unit flows a current in the direction of the electromagnet coil in the direction of the electromagnet coil in the direction of the electromagnet coil 7 for the first base sequence T, and generates an N pole in the electromagnet. S poles can be generated.
  • the current flows in the direction of the electromagnet coil 8 in the counterclockwise direction adjacent to C, the second base sequence of the sense strand, so that the N pole is generated in the electromagnet and the S pole is generated in the electromagnet.
  • the same A electromagnet pair as the first base sequence T is used for the seventh base sequence C of the sense strand.
  • the current flows in the direction of the electromagnet coil from the electromagnet coil in the direction of the electromagnet coil, thereby generating the N pole in the electromagnet and the S pole in the electromagnet.
  • the electromagnet drive unit sends current in the direction of the electromagnet coil from the electromagnet coil to the electromagnet coil, whereby the N pole is generated from the electromagnet and the S pole is Can produce
  • the first base of the antisense strand current can flow from the pair of electromagnets in the direction of 6 electromagnet coil to 12 electromagnet coil so that N pole is generated at 6 electromagnet and S pole is generated at electromagnet. have. This may be in the same current direction as A, the last nucleotide sequence of the sense strand.
  • the second base of the antisense strand In order to drive the polar magnetic field of C, the second base of the antisense strand, current flows from the pair of electromagnets adjacent to each other in the clockwise direction 5 from the electromagnet coil to the direction of the electromagnet coil. I can drive it.
  • the current is continuously flowed from 1 electromagnet coil in the direction of electromagnet coil 7 in the direction of electromagnet coil 1 1 N pole is generated from electromagnet and 7 electromagnet It can be driven by creating the S pole.
  • the magnetic field generated by the electromagnet pair thus driven becomes the polar magnetic field of the target DNA at the virtual circle center where the electromagnets are arranged. Therefore, if the target DNA is located at the virtual circle center, the target DNA is located in the polar magnetic field environment.
  • the number of electromagnets can be set within the range of 6 to 14 described above so that a desired effect is derived according to the structure of the DNA double helix.
  • the driving time of the electromagnet pair may be different depending on the DNA base pair.
  • the driving time of the electromagnet pairs driven simultaneously at the time point is the same, and the time may be selected within the range of 10 msec or more and 300 msec or less. In this case, the selected driving time may be equally applied to all electromagnets or may be differently applied.
  • the ratio of T (thymine): A (adenine) base pair to the C (cytosine): G (guanine) base pair constituting the target DNA base pair is 30 to about 3/4. It may have a: 60 or 60: 80msec drive time.
  • the driving time of the DNA base pairs may vary depending on the nucleotide sequence of the DNA double helix
  • a simple in vitro experiment using the target DNA double helix is used to select a DNA base pair driving time suitable for the target DNA nucleotide sequence before performing gene regulation. Can be.
  • the magnetic field generated from the plurality of electromagnets may be focused at a point on a virtual straight line perpendicular to the center of the circle in which the electromagnets are arranged.
  • the head of the human body is at the center of the circle, and the abdomen portion, which is the actual target position, may be protruded with respect to the center of the circle.
  • the abdominal region may be targeted by changing the orientation angle of the electromagnet to target the abdominal region.
  • the entire electromagnet may exhibit a funnel shape.
  • the direction angle change of the electromagnet may be made in the electromagnet driving unit or may be made in the electromagnet posture controller provided separately.
  • the polar magnetic field or the semipolar magnetic field generated by the hydrocephalus gene regulator of the present invention may be applied to an organism including the target DNA, and thus may have an intensity that does not harm the organism.
  • the intensity of the magnetic field generated at the center of each pair of electromagnets may be 50 ⁇ T to 1T.
  • 50 ⁇ T is the strength of weak magnetic field, it is enough to affect the hydrogen bond which is the actual target of polar magnetic field.
  • the magnetic field strength of 1T can be the magnetic field that can activate target DNA in a short time.
  • the electromagnet driver 130 sequentially drives the electromagnet pair in one of the clockwise or counterclockwise direction.
  • the electromagnet driving unit may drive only a pair of electromagnets at a time point, and may not drive other electromagnets.
  • the electromagnet drive unit delimits the pair of electromagnets with a polar or semipolar magnetic field corresponding to the base sequence of the first strand.
  • the polar magnetic field may drive the pair of electromagnets in the second direction from the first base sequence to the final base sequence of the second strand.
  • the first direction may be counterclockwise and the second direction may be clockwise. Of course, the opposite is also possible.
  • a strong polar magnetic field or a semipolar magnetic field environment for the target DNA is generated compared to the target strand of either the sense strand or the antisense strand.
  • the one-time continuous irradiation of the polar magnetic field or the semipolar magnetic field with respect to the sense strand and the antisense strand with respect to the same DNA double helix can be referred to as one-time driving.
  • the DNA double helix is distributed evenly in the upright or inverted direction.
  • the nucleotide sequences are arranged clockwise, and in the inverted DNAs, the nucleotide sequences are counterclockwise.
  • One driving start direction may include both the counterclockwise and clockwise directions of the DNA double helix.
  • the electromagnet drive unit may repeat the one-time driving of the target DNA a plurality of times. According to this, the effect of gene regulation can be enhanced by accumulating the electrostatic charge of the DNA base pair hydrogen bonds generated by the hydrolysis reaction in the target DNA nucleic acid.
  • the above one-time operation can be repeated for 1-100 minutes.
  • the polar magnetic field or the semi-polar magnetic field environment generated by the above configuration is located in an upright state in which the target DNA double helix shown in FIG. 7 is orthogonal to the virtual circle (xz plane) in which the electromagnet pairs are arranged, and the direction of each base pair is an electromagnet. It is assumed that it matches the direction of the pair. However, since the target DNA double helix can be located in various states, even if the target DNA is located in the imaginary circle center where the pairs of electromagnets are arranged, the polar magnetic field or the semipolar magnetic field environment generated by the above configuration may be a polar magnetic field or It may not be a semipolar magnetic field.
  • Genetic regulation may be performed by shifting the one-time driving position to a polar or semipolar magnetic field generated in an electromagnet pair to obtain a gene regulatory effect on a larger number of target DNAs.
  • the alignment directions may correspond to each other.
  • the base sequence TCAGCACGATGA of the target DNA is driven with the NNSSNSNSSNSS polarity starting from the electromagnet 1 assuming a state starting from the direction of the electromagnet 1, and the probability that the base sequence of the target DNA is arranged from the direction of the electromagnet 1 is Relatively low.
  • the electromagnet pairs 1-7 were arbitrarily selected as driving start electromagnet pairs.
  • the reason for arbitrarily selecting the driving start electromagnet pairs is that the starting position of the actual nucleotide sequence in the target DNA is unknown.
  • the electromagnet driver 130 starts a new drive of the pair of electromagnets that are adjacent to the previous drive initiation electromagnet pair in the counterclockwise or clockwise direction after the first drive on the target DNA.
  • the one-time driving may be repeated by the number of electromagnet pairs (half the number of electromagnets) as the electromagnet pairs. This allows gene regulation on more target DNAs.
  • the one time driving completion time may be the driving completion time of the electromagnet pair for one strand or the driving completion time of the electromagnet pair for both strands.
  • a new drive start electromagnet pair is selected after the set time elapses.
  • the driving start electromagnet pair is changed as follows.
  • the A electromagnet pair (1-7) is driven with respect to the DNA double helix, and once the drive is repeated for about 1-100 minutes, the B electromagnet pair (2-8) adjacent in the counterclockwise direction is newly replaced.
  • the said one time drive is performed by the same method as a drive start electromagnet pair.
  • the new electromagnetization starting electromagnet pair (3-9) is returned to the counterclockwise direction.
  • the single run is performed continuously in pairs for about 1-100 minutes.
  • the positional movement of the single drive may be equal to the number of electromagnet pairs.
  • the bases of the sense strand and the bases of the antisense strand have complementary nucleotide sequences, but the polar or semipolar fields of the base of the sense strand and the antisense strand in the DNA double helix base pair are always constant. .
  • the polar or semipolar magnetic field corresponding to the base sequence of the sense strand and the polar or semipolar magnetic field of the antisense strand are the same.
  • antisense that is complementary from the nucleic acid of the last nucleotide sequence of the sense strand is driven counterclockwise in the order of the polar or semipolar magnetic field corresponding to the sense strand nucleotide sequence of the target DNA double helix.
  • the base sequence can be driven sequentially in the clockwise direction with the same polar or semipolar magnetic field.
  • the sense base of the DNA base pair is connected to opposing electromagnets connected in series or in parallel along the polar direction of the same electromagnet coil.
  • Current direction should be used to create a magnetic field consistent with the polarity of the sequence and antisense sequence.
  • the current direction control of the electromagnet is made by the electromagnet driver.
  • the hydrogen bond which is an intermolecular bond
  • the hydrogen bond is excessively biased to one side.
  • an intermolecular secondary structure may occur due to memory phenomenon caused by excessively induced electrostatic charge.
  • the target DNA is continuously activated by the polar magnetic field, thereby reducing the inherent reducing power of DNA.
  • mRNA transcription may not occur due to specific transcription factors, DNA replication enzymes, or other DNA attachment proteins, and cation salts such as histones, polyamines, and Ca ++ and Mg ++ scattered around the target DNA are strongly attached. Rather, target DNA function can be inhibited.
  • the auxiliary electromagnet 150 is used for the generation and irradiation of the reducing magnetic field.
  • the genetic regulator as shown in FIG. 4 is a hypothetical orthogonal to the virtual circle center.
  • Two auxiliary electromagnets (vertical electromagnets) are further arranged on both sides of the line, and the electromagnet drive unit drives the auxiliary electromagnet so that a magnetic field is irradiated to the center of the pair of electromagnet pairs arranged in a circular shape after the single drive on the target DNA double helix. You can.
  • the distribution of the DNA double helix in three-dimensional space can be analyzed by a spherical coordinate system.
  • (X, y, z) (rsin ⁇ cos ⁇ , rsin ⁇ sin ⁇ , rcos ⁇ ), 0 ⁇ ⁇ ⁇ 2 ⁇ , 0 ⁇ ⁇ , r> 0.
  • r is the radius of the sphere
  • ⁇ is the angle tilted from the Z axis
  • ⁇ is the angle rotated from the X axis.
  • the DNA double helix has bidirectional polarity in the sense and antisense directions, and since both DNA strands are hybridized by base pairs, the genetic regulator has a polar or semipolar magnetic field for both the sense and antisense strands of the target DNA double helix. Performing a simulation can be effective.
  • the polar magnetic field can cause a proton spin of the hydrogen atoms in the base-pair hydrogen bonds, the proton spin phenomenon will disappear immediately after the magnetic field disappears.
  • the electron spin perturbation of the outer electrons caused by the proton spin causes the precession of electrons, and the change of the outer electron orbit appears as the molecular polarity change of the attached hydrogen compound by polarizing the hydrogen atom, which is the original state. It can not be recovered and is delayed for some time.
  • the time when the phase change of the hydrogen atom caused by the magnetic field in the molecular structure returns to its original state immediately after the disappearance of the magnetic field can be measured as the T2 relaxation time in the NMR measurement.
  • the T2 relaxation time of water molecules is about 0.25 seconds (about 250 msec).
  • the water molecules are in a very irregular arrangement, and since one water molecule has hydrogen bonds with two or three different water molecules, the hydrogen bonds act in combination.
  • the NMR values of water represent the mean T2 relaxation time of hydrogen atoms hydrogenated in various directions, so that the T2 relaxation time of hydrogen atoms in hydrogen bonds parallel to the magnetic field can be much higher than about 250 msec.
  • Base pair hydrogen bonds of DNA double helix can occur in aqueous solution. It is very difficult to measure T2 relaxation time of DNA double helix only in aqueous solution, so the T2 relaxation time of DNA double helix is about 0.3 seconds longer than that of water molecules. (About 300 msec) can be estimated.
  • the irradiation time period of the polar magnetic field for each DNA base pair should take into account the phase change of the hydrogen atoms for the front and back nucleotide sequences simultaneously in the DNA double helix. Therefore, the maximum irradiation time period should be approximately 0.3 seconds (the expected T2 relaxation time of the DNA double helix). About 300 msec), and the minimum time to create a polar magnetic field for the electromagnet coil to be set to 0.01 seconds (about 10 msec), and about 0.01-0.3 seconds (about 10-300 msec) for each target DNA sequence. Irradiation time periods may be used.
  • an electric field shielding film including a nonmagnetic metal By installing an electric field shielding film including a nonmagnetic metal on the imaginary circle center or around the base pair where the electromagnet pairs are disposed, interference of an electric field introduced from the outside or generated in the electromagnet driver may be minimized.
  • the effect of the electric field is relatively small in the hydrosensor response gene regulator can be performed mainly through the effect of the magnetic field (magnetic effect).
  • the electronic device may further include an electromagnetic field shielding film that shields a magnetic field scattered to the outside of the magnetic field generated by the electromagnet and shields an electric field flowing from the outside of the virtual circle.
  • it may further include a cooling device for reducing the heat generated by the electromagnet drive.
  • Oligo DNA double helix 6T6A, 6T6A and 11C1A ⁇ 1T11G were irradiated with a polar magnetic field corresponding to each nucleotide sequence.
  • the irradiation time period of the polar magnetic field was increased by 5 msec from 10 msec to 90 msec for 30 minutes, and the polar magnetic field coinciding with the oligo DNA double helix was examined.
  • the oligo DNA double helix was separated through HPLC using a Diol 300 (YMC, USA) column, and the absorbance of UV 260 was measured to analyze the size of the DNA peak.
  • the UV 260 absorbance at 6T6A and 6T6A increased gradually from the 10msec irradiation time period, resulting in maximum UV 260 absorbance at 50msec and then decreasing.
  • T: A base pairs are activated, the large major grooves of the DNA double helix and the small minor grooves become smaller, thus increasing the shape of the DNA double helix and increasing UV 260 absorbance.
  • 6T6A ⁇ 6T6A has the largest activation of DNA double helix due to polar magnetic field at 50msec irradiation period.
  • the UV 260 absorbance gradually increased from the 10 msec irradiation time period, and the maximum UV 260 absorbance was decreased after 80 msec. This can be seen that the base pair is activated by the polar magnetic field in 11C1A.1T11G to reduce the quadruple formation in the 80msec irradiation time period.
  • the ratio of the magnetic field irradiation time periods of the T: A base pair and the C: G base pair may be about 1/2 to 3/4. have.
  • T A base pair is arbitrarily selected using a polar magnetic field irradiation time period of about 30-60 msec and C: G base pair is approximately.
  • the polar magnetic field irradiation time period of about 60 ⁇ 90msec can be selected arbitrarily.
  • the structure and function of the DNA double helix can be regulated by activating the magnitude of the hydrogen bonding force of the base pairs regularly arranged in the center of the DNA double helix, and the corresponding gene can be activated or inactivated.
  • the polar magnetic field for the target DNA code can act nonspecifically on other DNA codes and a nonspecific magnetic field can be generated in the coils that form the electromagnets.
  • Figure 9 was carried out experiments to determine the effect of the gene regulatory action when cleaving the pBluescript SK (-), a plasmid DNA with XhoI DNA restriction enzyme.
  • pBluescript SK (-) was reacted with a XhoI enzyme in a buffer, and gene regulation using CTCGAG, which is an attachment sequence of XhoI, was performed.
  • CTCGAG which is an attachment sequence of XhoI
  • gene regulation using ACGTAC sequence not related to XhoI attachment sequence was performed, but no gene control was performed at all in the negative control group.
  • electrophoresis was performed using an agarose gel to confirm the cleaved DNA band by fluorescence reaction of ethidium bromide. Especially. When ethidium bromide is attached to the DNA, staining was observed before and after electrophoresis of DNA to discriminate errors due to nonspecific reactions (Fig. 9a).
  • the loose DNA produced when DNA restriction enzyme cuts the plasmid DNA has a higher absorbance (OD 260 ) in the ultraviolet spectrum than the twisted DNA. Quantitative analysis.
  • Figure 9b shows the standard increase pattern by HPLC analysis of the increase in absorbance (OD 260 ) of the ultraviolet spectrum generated when the DNA restriction enzyme cut the plasmid DNA
  • Figure 9c shows the restriction enzyme reaction in the experiment of Figure 9a of this experiment HPLC analysis of samples obtained at 10-minute intervals revealed that gene regulation (HMR-GR) was performed using CTCGAG, an XhoI-attached base sequence, or gene regulation was performed using ACGTAC, a random sequence. The DNA cleavage effect was faster and larger than in unregulated cases.
  • HMR-GR gene regulation
  • cancer cells generated in living organisms are inhibited by activating a plurality of cancer suppressor genes involved in the gene regulator of the present invention, ie, increasing expression, and inhibiting the growth of cancer cells by increasing the expression of apoptosis-related genes for cancer cells.
  • Animal experiments were conducted on obtaining cancer treatment effects by inducing their apoptosis.
  • chemotherapy was performed for prostate cancer in humans transplanted into nude mice.
  • Human prostate carcinoma (DU145, ATCC) was implanted in nude mice, and when cancer masses grew to about 5 mm, 10 mm and 20 mm in size, chemotherapy was performed with gene regulators, respectively.
  • the target DNA used for gene therapy is human p53, BAX, NOXA, TGF ⁇ , and PTEN.
  • p53 is an anticancer gene that inhibits the proliferation of cancer cells and BAX and NOXA apoptosis cancer cells.
  • TGF ⁇ can inhibit canceration by promoting cell differentiation of cancer cells
  • PTEN is a potent anticancer gene that regulates the signaling system.
  • the genBank database was searched to obtain about 2000bps of the promoter region of each target DNA, and the gene sequence was performed using a target DNA sequence of about 30-50bps.
  • 3-5 transcription factor attachment domains were found at the promoter region of a single gene, and gene regulators were applied by circulating the target DNA sequences in each gene in order.
  • mice were bred in a sterile filter breeding box in a conventional manner, and put into a plastic round barrel having a diameter of about 8cm and used a genetic regulator including up to an auxiliary electromagnet (150).
  • a genetic regulator including up to an auxiliary electromagnet (150).
  • nude mice are frequently moved in plastic barrels, so the nuds are not located in the center of the virtual circle where the lumps of electromagnets are arranged. That is, the gene regulator was driven for about 6-8 hours a day, and after about 10 days, the mass was extracted and histological observations were performed.
  • the nucleus size was significantly reduced in the nude mouse irradiated with the polarized magnetic field (PMF) after visual observation after applying the polar magnetic field using the BAX and NOXA genes as target DNA for 10 days. It became.
  • PMF polarized magnetic field
  • Figure 10 is a schematic diagram showing the experimental results of applying a gene regulator as the initial carcinoma of humans with a diameter of about 3 mm and the mass of the prostate carcinoma after implantation of human prostate carcinoma subcutaneously, such as nude mice.
  • Tissue specimens were cut and cut in half, and the specimens were prepared and examined under a microscope.
  • the random sequence GR was irradiated at low magnification, the cancer mass was filled with cancer cells, but the reverse PMF GR was examined. There was a significant reduction in the number of cancer cells in the mass, and when the polar magnetic field (PMF GR) was examined, some of the remaining cancer cells gathered in the center as the mass was almost extinguished and replaced with fibrous granulation tissue.
  • PMF GR polar magnetic field
  • the random magnetic field was highly malignant in cancer cells, causing severe proliferation and irregular nuclei.
  • the cancer cells were well distributed around the blood vessels in the mass, but the proliferation was slightly decreased, and the apoptosis was partially increased.
  • the polar magnetic field was examined, the malignancy of the remaining cancer cells was almost disappeared, but rather, the mononuclear shape and the distribution of the nucleus were similar to those of the benign tumor cells.
  • Figure 11 shows random GR, reverse PMF, and polar magnetic field (PMF) for mid-term carcinomas of about 1 cm in diameter in human prostate carcinomas implanted in nude mice. ) Schematic diagram showing the results of experiments divided into groups.
  • the nucleus of the nude mouse irradiated with the semipolar magnetic field did not increase significantly, but the proliferation of the mass was asymmetric.
  • the random magnetic field of the extracted cancer mass was filled with highly proliferative malignant cancer cells.
  • necrosis by partial apoptosis was frequently observed in cancer tissues, and malignant cancer cells were frequently observed.
  • Immunohistochemical staining of PCNA, p53, BAX, NOXA, and PARP showed positive responses in random and semipolar or polar magnetic fields. Compared to the random magnetic field, the positive polarity of p53, BAX, NOXA, and PARP was increased in the cancer cells in the site of necrosis caused by apoptosis. In the case of the polar magnetic field, p53, BAX, NOXA, and PARP were positively detected in the cancer cells of the cystic degeneration site with multiple apoptosis inside the cancer tissue.
  • the positive response of p53, BAX, and NOXA was stronger in the immunohistochemical staining than in the case of random and semipolar magnetic fields, which suppressed the growth of p53 / BAX / NOXA cancer cells. It is determined that the signaling pathway is activated.
  • Figure 12 is a schematic diagram showing a state in which a gene regulator is applied to a terminal cancer mass grown to a diameter of about 2 cm large by implanting human prostate cancer cells (DU-145) into the shoulder subcutaneous tissue of nude mice.
  • Figure 13 is a flow chart showing the gene regulation method of the present invention.
  • the gene regulation method shown in FIG. 13 can be described as the operation of the gene regulator shown in FIG. 5, in particular the electromagnet drive.
  • the driving step disclosed in FIG. 13 (S 520) is driven in a sequential order in a counterclockwise direction using a polar magnetic field or a semipolar magnetic field according to the polarity of the sense strand base sequence of the DNA double helix (S 520), and the sense strand base
  • the target DNA double helix further includes a reverse driving step (S 530) which is driven in sequence in the clockwise direction using a polar magnetic field or a semipolar magnetic field according to the polarity of the base sequence of the antisense strand from the completion of driving of the sequence. It may include the step of completing the one-turn drive for.
  • the one-time driving may be repeated for a predetermined time, and when the one-time driving repeat is completed, the driving step (S520) using an electromagnet adjacent to the driving start electromagnet in the driving step (S520) as a new driving start electromagnet. ) And repeating the reverse driving step (S 530) by the number of electromagnet pairs (S 540).
  • a selection step of selecting one of the polar magnetic field and the semi-polar magnetic field, and one or both of the sense strand and the antisense strand may be further included.
  • the number of repetitions or the driving time of one driving may be further selected.
  • the target DNA is uniformly distributed in the upright or inverted direction in the three-dimensional space, it is possible to select both the counterclockwise or clockwise direction in the S520 driving step.
  • the opposite direction of the S520 driving step should be selected.
  • the driving step [S510- (S520-Repeat-S530) -S540] disclosed in FIG. 13 is a method for one target DNA, and when the target DNA is plural, the driving step is first performed for each one driving. Can be repeated again.
  • the gene control method disclosed above can be recorded as a program through a computer-readable medium.
  • the gene regulator of the present invention can be applied to a device for activating or deactivating various genes of organisms composed of DNA / RNA including hydrogen bonds.
  • it can be used to treat various malignancies such as cancer, stem cell treatment, and endocrine genetic material control.
  • activation of the target DNA according to the present invention is independent of chemical action, it can be applied in parallel with various drugs or physicochemical methods that have little direct relation to the mechanism of action.
  • the gene regulation method When the gene regulation method is applied, it is very unlikely to cause genetic mutations, so it can be used safely. Since the magnetic field having high permeability to the object is used, the target site is easily accessible and non-destructive, so it can be used in a variety of ways and widely.

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Abstract

Selon la présente invention, l'invention concerne un régulateur génique de réaction magnétique de l'hydrogène comprenant : des électroaimants en nombre pair disposés à des intervalles équidistants à l'intérieur d'un cercle virtuel de sorte qu'ils génèrent des champs magnétiques aptes à simuler une structure d'ADN à double hélice ; et une unité d'entraînement d'électro-aimant qui entraîne séquentiellement une paire d'électro-aimants opposés à partir desdits électro-aimants, selon une séquence de base d'un brin sens ou d'un brin antisens dans une paire de bases d'une double hélice d'ADN cible, utilisant une polarité qui génère des champs magnétiques polaires ou semi-polaires correspondant à la paire de bases de la double hélice d'ADN cible. Par conséquent, le régulateur de la présente invention peut générer des champs magnétiques polaires ou semi-polaires aptes à activer ou d'inactiver des gènes.
PCT/KR2012/005790 2011-07-19 2012-07-19 Régulateur génique d'une réaction magnétique de l'hydrogène et procédé de régulation génique Ceased WO2013012276A2 (fr)

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