CA2090355A1 - Method of Gene Transfer Using Galactosylated Histones - Google Patents
Method of Gene Transfer Using Galactosylated HistonesInfo
- Publication number
- CA2090355A1 CA2090355A1 CA 2090355 CA2090355A CA2090355A1 CA 2090355 A1 CA2090355 A1 CA 2090355A1 CA 2090355 CA2090355 CA 2090355 CA 2090355 A CA2090355 A CA 2090355A CA 2090355 A1 CA2090355 A1 CA 2090355A1
- Authority
- CA
- Canada
- Prior art keywords
- protein
- cells
- genetic
- histone
- galactosylated
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 108090000623 proteins and genes Proteins 0.000 title abstract 11
- 108010033040 Histones Proteins 0.000 title abstract 4
- 238000000034 method Methods 0.000 title abstract 3
- 102000006947 Histones Human genes 0.000 title 1
- 102000004169 proteins and genes Human genes 0.000 abstract 8
- 210000004027 cell Anatomy 0.000 abstract 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 abstract 2
- 210000003855 cell nucleus Anatomy 0.000 abstract 2
- 230000014509 gene expression Effects 0.000 abstract 2
- 238000001727 in vivo Methods 0.000 abstract 2
- 102100027211 Albumin Human genes 0.000 abstract 1
- 108010088751 Albumins Proteins 0.000 abstract 1
- 102000052510 DNA-Binding Proteins Human genes 0.000 abstract 1
- 101710096438 DNA-binding protein Proteins 0.000 abstract 1
- 108090000288 Glycoproteins Proteins 0.000 abstract 1
- 102000003886 Glycoproteins Human genes 0.000 abstract 1
- 208000026350 Inborn Genetic disease Diseases 0.000 abstract 1
- 241001465754 Metazoa Species 0.000 abstract 1
- 108010008699 Mucin-4 Proteins 0.000 abstract 1
- 102100022693 Mucin-4 Human genes 0.000 abstract 1
- 208000009869 Neu-Laxova syndrome Diseases 0.000 abstract 1
- 108010077850 Nuclear Localization Signals Proteins 0.000 abstract 1
- 208000037273 Pathologic Processes Diseases 0.000 abstract 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract 1
- 230000008878 coupling Effects 0.000 abstract 1
- 238000010168 coupling process Methods 0.000 abstract 1
- 238000005859 coupling reaction Methods 0.000 abstract 1
- 210000004748 cultured cell Anatomy 0.000 abstract 1
- 238000009792 diffusion process Methods 0.000 abstract 1
- 229930182830 galactose Natural products 0.000 abstract 1
- 238000001476 gene delivery Methods 0.000 abstract 1
- 208000016361 genetic disease Diseases 0.000 abstract 1
- 230000002068 genetic effect Effects 0.000 abstract 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 abstract 1
- 210000003494 hepatocyte Anatomy 0.000 abstract 1
- 239000012528 membrane Substances 0.000 abstract 1
- 238000005580 one pot reaction Methods 0.000 abstract 1
- 230000009054 pathological process Effects 0.000 abstract 1
- 230000035790 physiological processes and functions Effects 0.000 abstract 1
Classifications
-
- 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
Landscapes
- Genetics & Genomics (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to the field of introducing genetic material to cultured cells and into cells of animals in vivo. In particular, the invention relates to the use of receptor-targeted neoglycoprotein to carry genetic material into cells. The invention also uses nuclear-localization signals(Gerace et al. Annu. Rev. Cell Biol.
1988, 4:335-374), to facilitate the entry of genetic materials into cell nucleus for gene expression. The present invention has a wide variety of applications, for example, in treatment of genetic diseases, in study of cell biology, and in genetic interventions of physiological and pathological processes. The present invention is a effective method for introducing and expressing genes in hepatoma cells and hepatocytes in vivo. Its design has several novel features. First, this invention uses a simple coupling reagent (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide) to chemically add galactose to a protein, histone, in a one step reaction. The galactosylated protein (for example, albumin, histone and any other protein) has high affinity for the ASGP receptor; Second, the invention uses a protein which is a natural DNA-binding protein; Three, this invention uses a protein which crosses the membranes of cell nucleus by a facilitated process in addition to simple diffusion. This feature contributes greatly to the high level expression of the introduced foreign genes; Last, the galactosylated histone 1 is the physical embodiment of all the features in this invention. This means this gene delivery system has only one component and is simple, reliable, and efficient from engineering-design point of view.
1988, 4:335-374), to facilitate the entry of genetic materials into cell nucleus for gene expression. The present invention has a wide variety of applications, for example, in treatment of genetic diseases, in study of cell biology, and in genetic interventions of physiological and pathological processes. The present invention is a effective method for introducing and expressing genes in hepatoma cells and hepatocytes in vivo. Its design has several novel features. First, this invention uses a simple coupling reagent (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide) to chemically add galactose to a protein, histone, in a one step reaction. The galactosylated protein (for example, albumin, histone and any other protein) has high affinity for the ASGP receptor; Second, the invention uses a protein which is a natural DNA-binding protein; Three, this invention uses a protein which crosses the membranes of cell nucleus by a facilitated process in addition to simple diffusion. This feature contributes greatly to the high level expression of the introduced foreign genes; Last, the galactosylated histone 1 is the physical embodiment of all the features in this invention. This means this gene delivery system has only one component and is simple, reliable, and efficient from engineering-design point of view.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2090355 CA2090355C (en) | 1993-02-25 | 1993-02-25 | Method of gene transfer using galactosylated histones |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2090355 CA2090355C (en) | 1993-02-25 | 1993-02-25 | Method of gene transfer using galactosylated histones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2090355A1 true CA2090355A1 (en) | 1994-08-26 |
| CA2090355C CA2090355C (en) | 1997-04-08 |
Family
ID=4151204
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2090355 Expired - Fee Related CA2090355C (en) | 1993-02-25 | 1993-02-25 | Method of gene transfer using galactosylated histones |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2090355C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001076638A3 (en) * | 2000-04-12 | 2002-05-16 | Implyx Ltd | Compositions for drug delivery |
-
1993
- 1993-02-25 CA CA 2090355 patent/CA2090355C/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001076638A3 (en) * | 2000-04-12 | 2002-05-16 | Implyx Ltd | Compositions for drug delivery |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2090355C (en) | 1997-04-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |