ES2660846T3 - Composiciones poliplex de quitosano-ácido nucleico de alta concentración - Google Patents
Composiciones poliplex de quitosano-ácido nucleico de alta concentración Download PDFInfo
- Publication number
- ES2660846T3 ES2660846T3 ES08833604.5T ES08833604T ES2660846T3 ES 2660846 T3 ES2660846 T3 ES 2660846T3 ES 08833604 T ES08833604 T ES 08833604T ES 2660846 T3 ES2660846 T3 ES 2660846T3
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- nucleic acid
- polypelex
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- high concentration
- chitosan
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- 239000000203 mixture Substances 0.000 title abstract description 8
- 229920001661 Chitosan Polymers 0.000 abstract description 6
- 238000004220 aggregation Methods 0.000 abstract description 3
- 230000002776 aggregation Effects 0.000 abstract description 3
- 239000003112 inhibitor Substances 0.000 abstract 2
- 150000007523 nucleic acids Chemical class 0.000 abstract 2
- 102000039446 nucleic acids Human genes 0.000 abstract 2
- 108020004707 nucleic acids Proteins 0.000 abstract 2
- 239000002244 precipitate Substances 0.000 abstract 1
- 239000004743 Polypropylene Substances 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229920001296 polysiloxane Polymers 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000002572 peristaltic effect Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 102100024321 Alkaline phosphatase, placental type Human genes 0.000 description 1
- 241000283724 Bison bonasus Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 101000620653 Homo sapiens Serine/threonine-protein phosphatase 5 Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- ZYFVNVRFVHJEIU-UHFFFAOYSA-N PicoGreen Chemical compound CN(C)CCCN(CCCN(C)C)C1=CC(=CC2=[N+](C3=CC=CC=C3S2)C)C2=CC=CC=C2N1C1=CC=CC=C1 ZYFVNVRFVHJEIU-UHFFFAOYSA-N 0.000 description 1
- 102100022346 Serine/threonine-protein phosphatase 5 Human genes 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 108010089807 chitosanase Proteins 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- QYSGYZVSCZSLHT-UHFFFAOYSA-N octafluoropropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)F QYSGYZVSCZSLHT-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 108010031345 placental alkaline phosphatase Proteins 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- -1 polypropylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/02—Heterocyclic radicals containing only nitrogen as ring hetero atoms
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
Abstract
Una composición que comprende poliplex de quitosano-ácido nucleico hidratados y estables y un inhibidor de agregación, en el que dicha composición tiene una concentración de ácido nucleico mayor que o igual a 0.5 mg/ml, y dicha composición está libre de precipitado de poliplex, y además dicho inhibidor de agregación es un azúcar
Description
Los compuestos de la invención también se pueden administrar directamente al ojo u oído, típicamente en forma de gotas. Otras formulaciones adecuadas para la administración ocular y auditiva incluyen ungüentos, implantes biodegradables (por ejemplo, esponjas de gel absorbibles, colágeno) y no biodegradables (por ejemplo, silicona), obleas, lentes y sistemas de partículas. Las formulaciones también pueden administrarse por iontoforesis.
5 Las formulaciones para administración ocular/aural se pueden formular para que sean de liberación inmediata y/o modificada. Las formulaciones de liberación modificada incluyen liberación retardada, sostenida, pulsada, controlada, dirigida o programada.
Ejemplo 1: Preparación poliplex de hasta 250 µg/ml seguido de concentración hasta >1 mg/ml.
Ver figura 1 y descripción a continuación para descripciones a modo de ejemplo de reactivos, concentraciones y 15 proporciones.
Se probó un simple aparato de mezclado en línea a pequeña escala utilizando bombas de jeringa y bombas peristálticas de alta velocidad, tubos de silicona y uniones en T de polipropileno. Este proceso se usó para hacer poliplex con una concentración final de ADN de hasta 250 µg/mL con una proporción N/P de 20 utilizando 20 23mero/98% de DDA quitosano (es decir, polímeros de quitosano con un promedio de 23 monómeros (glucosamina), y 98% de desacetilación). Los resultados mostraron que el tamaño de partícula y el PDI de los poliplex podían controlarse estrechamente controlando las concentraciones de materia prima, las proporciones de mezcla volumétrica y las velocidades de flujo de las soluciones de ADN y quitosano. Además, se encontró que la incorporación de sacarosa en las materias primas de ADN y quitosano ayudaba al proceso de fabricación al reducir
25 el tamaño de partícula y PDI. La inclusión de sacarosa también evitó la agregación de partículas durante el proceso de concentración. Los poliplex congelados con una concentración de ADN de aproximadamente 1 mg/mL y que contienen hasta un 15% de sacarosa fueron estables durante al menos 1 mes. Además, el proceso de mezcla en línea se ajustó fácilmente desde 50 mL hasta 2 L con valores bajos de desviación estándar relativa (RSD): tamaño de partícula = ±9%, PDI = ±6%.
30
- Material
- Proveedor Catálogo #
- Quitosano (23 mer, 98% DDA)
- Biosyntech N/A
- pADN (pCHS4-3xFLAG-CMV-SEAP-attB)
- enGene Inc. N/A
- pADN (pCMV-INT)
- enGene Inc. N/A
- pADN (gWIZ-SEAP)
- Aldevron LLC 5005
- pADN (gWIZ-Luciferasa)
- Aldevron LLC 5001
- Sacarosa, grado ACS
- Fisher Scientific S5-3
- Tubo de silicona curado con Pt, 1/16 “ID
- Cole-Parmer 95802-02
- Conexiones en T PP, ID de 3/32 “
- Cole-Parmer 30623-57
- Jeringas PP, 3 mL
- B-D 309585
- Jeringas PP, 10 mL
- B-D 309604
- Jeringas PP, 20 mL
- B-D 309661
- Jeringas PP, 30 mL
- B-D 309650
- Conexiones Luer PP, ID de 1/8“
- Cole-Parmer 45500-04
- Filtros de jeringa de 25 mm, membrana Supor de 0.2 µm
- Pall 4612
- Filtros de jeringa de 32 µm de membrana de Supor 0.2 µm
- Pall 4652
- Cubetas desechables, PS, semi-micro de 1.5 ml
- Plastibrand 759075D
13
- Células Zeta capilares dobladas
- Malvern Instruments DTS 1060
- Cartucho TFF, 73 cm2, 1 mm ID, 100K MWCO
- GE Healthcare 56-4101-14
- Material
- Proveedor Catálogo #
- Cartucho TFF, 850 cm2, 1 mm ID, 100K MWCO
- GE Healthcare 56-4102-15
- Cartucho TFF, 73 cm2, 1 mm ID, 500K MWCO
- GE Healthcare 56-4101-18
- Kit de ensayo PicoGreen Quant-iT ds DNA HS
- Invitrogen Q32854
- enzima EcoR1, 20,000 U/mL
- New England BioLabs R0101S
- Tampón EcoR1, 10X
- New England BioLabs B0101S
- Enzima quitosanasa, 62 U/mL
- Sigma C0794
- Escalera de ADN superentorchada
- Invitrogen 15622-012
- tampón de carga Cian/Amarillo, 6X
- Invitrogen 10482-035
- Bromuro de Etidio
- EM Science 4410
- Agarosa, Ultra-Pura
- Invitrogen 15510-027
- Línea xcelular 293T-K
- Dr. Kieffer at UBC N/A
- Medio Eagle modificado por Dulbecco
- VWR X16777-128
- Suero Bovino fetal
- Wisent 080150
- Penicilina/Estreptomicina
- Invitrogen 15140-122
- Solución salina amortiguada por fosfato
- Invitrogen 21600-010
- Tripsina
- Invitrogen 25300-062
- Opti-mem
- Invitrogen 31985-070
- Ensayo quimioluminescente SEAP
- Roche 1779842
- Enzima de fosfatasa alcalina de la placenta
- Sigma P-3895
- Sero albúmina bovina (BSA)
- Sigma A9418
- Glicerol
- Sigma G5516
- Placa de 96 pozos de fondo plano blanca Microlite-1
- VWR 7417
- Equipo
- Fabricante
- Bomba de jeringa, NE-1000
- New Era Pump Systems Inc.
- Bomba de jeringa, NE-1000
- New Era Pump Systems Inc.
- Bombas peristálticas, Bomba Materflex L/S activada con cabezales de bomba L/S Easy-Load II
- Cole Parmer
- Medidor de tamaño de partícula Zetasizer Nano (ZEN 3600)
- Malvern Instruments
- pH Metro, Accumet AB15
- Fisher Scientific
- Espectrofotometro UV, Ultrospec 2100 pro
- Biochrom Ltd.
- Fluorómetro Qubit, cat # Q32857
- Invitrogen
14
Claims (1)
-
imagen1 imagen2
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US97631607P | 2007-09-28 | 2007-09-28 | |
| US976316P | 2007-09-28 | ||
| PCT/CA2008/001714 WO2009039657A1 (en) | 2007-09-28 | 2008-09-26 | High concentration chitosan-nucleic acid polyplex compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2660846T3 true ES2660846T3 (es) | 2018-03-26 |
Family
ID=40510712
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES08833604.5T Active ES2660846T3 (es) | 2007-09-28 | 2008-09-26 | Composiciones poliplex de quitosano-ácido nucleico de alta concentración |
Country Status (20)
| Country | Link |
|---|---|
| US (3) | US8722646B2 (es) |
| EP (1) | EP2195035B1 (es) |
| JP (2) | JP5650533B2 (es) |
| KR (2) | KR20100077155A (es) |
| CN (1) | CN101873867B (es) |
| AU (1) | AU2008302979B2 (es) |
| BR (1) | BRPI0817725A2 (es) |
| CA (1) | CA2700842C (es) |
| DK (1) | DK2195035T3 (es) |
| ES (1) | ES2660846T3 (es) |
| IL (1) | IL204677A (es) |
| MX (1) | MX2010003323A (es) |
| NO (1) | NO2195035T3 (es) |
| PL (1) | PL2195035T3 (es) |
| PT (1) | PT2195035T (es) |
| RU (1) | RU2010116775A (es) |
| SG (1) | SG187403A1 (es) |
| SI (1) | SI2195035T1 (es) |
| WO (1) | WO2009039657A1 (es) |
| ZA (1) | ZA201002169B (es) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5650533B2 (ja) * | 2007-09-28 | 2015-01-07 | エンジーン，インコーポレイティド | 高濃度キトサン−核酸ポリプレックス組成物 |
| CA2794923A1 (en) * | 2009-03-31 | 2010-10-07 | Engene, Inc. | Highly acidic chitosan-nucleic acid polyplex compositions |
| BR112013009934A2 (pt) | 2010-12-07 | 2016-07-05 | Hoffmann La Roche | dispositivo para adicionar pelo menos duas soluções de alimentação, aparelho de cultivo celular, uso de um dispositivo e método para obter um polipeptídeo |
| ES2635990T3 (es) * | 2012-03-21 | 2017-10-05 | Engene, Inc. | Nanopartículas de quitosano derivado dualmente y los métodos para fabricar y usar las mismas para la transferencia génica in vivo |
| ITTO20121107A1 (it) * | 2012-12-19 | 2014-06-20 | Idea Medical Devices S R L | Composizione a base di polidesossiribonucleotidi e relativi usi |
| EP3049473B1 (en) | 2013-09-25 | 2021-09-22 | Engene, Inc. | Dually derivatized chitosan nanoparticles and methods of making and using the same for gene transfer in vivo |
| WO2015125147A1 (en) | 2014-02-20 | 2015-08-27 | B. G. Negev Technologies And Applications Ltd | Anionic polyplexes for use in the delivery of nucleic acids |
| EP4353257A3 (en) | 2015-04-13 | 2024-08-07 | CureVac Manufacturing GmbH | Method for producing rna compositions |
| WO2017105138A1 (ko) * | 2015-12-18 | 2017-06-22 | 주식회사 삼양바이오팜 | 음이온성 약물을 함유하는 고분자 미셀의 제조방법 |
| KR101710639B1 (ko) * | 2016-06-07 | 2017-03-08 | 주식회사 파마리서치프로덕트 | 핵산, 키토산 및 히알루론산을 포함하는 조직 증강용 충전 조성물 및 이의 제조방법 |
| CN109310800B (zh) * | 2016-07-29 | 2022-01-07 | 医药研究有限公司 | 包含核酸和壳聚糖的肩袖撕裂修复用组合物 |
| EP3538659A4 (en) | 2016-11-09 | 2020-07-15 | Engene, Inc. | INTESTINAL EXPRESSION OF THE SCHEDULED DEATH LIGAND 1 |
| RU2697527C1 (ru) * | 2018-06-06 | 2019-08-15 | Федеральное государственное учреждение "Федеральный исследовательский центр "Фундаментальные основы биотехнологии" Российской академии наук" (ФГУ ФИЦ Биотехнологии РАН) | Иммуноадъювантная композиция для вакцин против инфекционных агентов вирусной и бактериальной природы |
| KR20210110791A (ko) * | 2018-12-28 | 2021-09-09 | 엠리트 제네틱스 리미티드 | 폴리플렉스의 형성 방법 |
| EP3693024A1 (en) * | 2019-02-05 | 2020-08-12 | Altona Diagnostics GmbH | Control for nucleic acid preparation and/or detection methods |
| US20220348900A1 (en) * | 2019-08-14 | 2022-11-03 | Modernatx, Inc. | Processes for purifying downstream products of in vitro transcription |
| WO2024219893A1 (ko) * | 2023-04-19 | 2024-10-24 | 주식회사 파마리서치 | 조직 수복용 조성물 |
| WO2026085495A1 (en) | 2024-10-18 | 2026-04-23 | Generation Bio Co. | Synthetic partially single-stranded nucleic acid compositions and uses and methods therefor |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6184037B1 (en) * | 1996-05-17 | 2001-02-06 | Genemedicine, Inc. | Chitosan related compositions and methods for delivery of nucleic acids and oligonucleotides into a cell |
| DE69712110T2 (de) * | 1996-07-10 | 2002-12-12 | West Pharmaceutical Services Drug Delivery & Clinical Research Centre Ltd., Nottingham | Zusammensetzungen zur einführung von genen in epithelzellen |
| EP1054694A2 (en) * | 1998-02-13 | 2000-11-29 | Selective Genetics, Inc. | Concurrent flow mixing methods and apparatuses for the preparation of gene therapy vectors and compositions prepared thereby |
| WO2000009086A2 (en) | 1998-08-14 | 2000-02-24 | Valentis, Inc. | Protected one-vial formulation for nucleic acid molecules, methods of making the same by in-line mixing, and related products and methods |
| US6251599B1 (en) * | 1998-11-06 | 2001-06-26 | Selective Genetics, Inc. | Stabilized nucleic acid compositions and methods of preparation and use thereof |
| DE10141971A1 (de) | 2001-08-28 | 2003-03-27 | Siemens Ag | Adaptive Kanalschätzung in einem OFDM-basierten Mobilfunksystem durch Variation der Anzahl der Pilotsymbole |
| EP1306127B2 (en) * | 2001-10-26 | 2011-09-07 | OctoPlus PolyActive Sciences B.V. | Method for the preparation of purified microparticles |
| NO317653B1 (no) * | 2002-05-03 | 2004-11-29 | Stiftelsen Biopolymer | Formulering som omfatter komplekser av kitosanoligomerer og nukleinsyre, fremgangsmate for a fremstille formuleringen samt anvendelser derav. |
| NO317654B1 (no) | 2002-05-03 | 2004-11-29 | Stiftelsen Biopolymer | Formulering som inneholder en nukleinsyre og et kitosan, fremgangsmate for fremstilling av formuleringen, samt anvendelser derav. |
| KR100613734B1 (ko) * | 2004-09-07 | 2006-08-22 | 굿젠 주식회사 | 키토산을 이용한 ｄｎａ 보관방법 및 분석방법 및 이를이용한 ｄｎａ 제품 |
| JP5650533B2 (ja) * | 2007-09-28 | 2015-01-07 | エンジーン，インコーポレイティド | 高濃度キトサン−核酸ポリプレックス組成物 |
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