Pharmaceutical composition useful for nucleic acid transfection,

Details Pharmaceutical composition useful for nucleic acid transfection, Pharmaceutical composition useful for nucleic acid transfection,

1998-03-27

2000-11-28

Guzo, David

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

4353201, 435455, 435458, 435325, 435366, 530350, 530358, 5303871, 5303873, 536 231, 536 235, 536 245, A61K 31711, A61K 317105

Patent

active

061535974

DESCRIPTION:

BRIEF SUMMARY
The present invention concerns the field of gene therapy and relates more particularly to the in vitro, ex vivo and/or in vivo transfer of genetic material. The invention proposes, in particular, a novel pharmaceutical composition which is useful for transfecting cells efficiently. The invention also relates to the uses of this composition.
Chromosomal deficiencies and/or anomalies (mutation, aberrant expression, etc.) are the cause of many diseases of hereditary or non-hereditary nature. Conventional medicine has for a long time remained powerless in respect of them. Today, with the development of gene therapy, it is hoped henceforth to be able to correct or prevent this type of chromosomal aberration. This novel medication consists in introducing genetic information into the affected organ or cell, for the purpose of correcting this deficiency or anomaly or alternatively for the purpose of expressing a protein of therapeutic interest.
The main obstacle to the penetration of a nucleic acid into a target organ or cell lies in the size and the polyanionic nature of this nucleic acid, which oppose its passage across cell membranes.
Various techniques are nowadays proposed to remove this difficulty including, more particularly, the transfection of naked DNA across the plasma membrane in vivo (WO90/11092) and the transfection of DNA via a transfection vector.
As regards the transfection of naked DNA, its efficacy still remains very low. Naked nucleic acids have a short plasma half-life on account of their degradation by enzymes and their elimination via the urine.
As regards the second technique, two main strategies are proposed: proposed to use adenoviruses, herpesviruses, retroviruses and more recently adeno-associated viruses. These vectors prove to be of high transfecting performance but it is unfortunately not possible to exclude entirely, as far as they are concerned, certain risks of pathogenicity, replication and/or immunogenicity, which are inherent in their viral nature. capable of promoting the transfer and expression of DNA in eukaryotic cells.
The subject of the present invention lies more particularly in this second strategy.
Chemical or biochemical vectors represent an advantageous alternative to natural viruses, in particular on account of this absence of viral recombination and/or immunological response. They possess no pathogenic power, there is no risk of DNA multiplication within these vectors and there is no theoretical limit associated with them as regards the size of DNA to be transfected.
These synthetic vectors have two main functions, to condense the DNA to be transfected and to promote its cellular binding as well as its passage across the plasma membrane and, where appropriate, the two nuclear membranes.
On account of its polyanionic nature, DNA naturally has no affinity for the plasma membrane of cells, which is also polyanionic in nature. To overcome this drawback, non-viral vectors all generally possess polycationic charges.
Among the synthetic vectors developed, cationic polymers of polylysine and DEAE-dextran type, or alternatively cationic lipids or lipofectants, are the most advantageous. They possess the property of condensing DNA and of promoting its association with the cell membrane. More recently, the concept has been developed of targeted transfection, mediated by a receptor. This technique exploits the principle of condensing DNA, by virtue of the cationic polymer, while at the same time directing the binding of the complex to the membrane using chemical coupling between the cationic polymer and the ligand for a membrane receptor which is present at the surface of the cell type which it is desired to graft. Targeting of the transferrin or insulin receptor or of the hepatocyte asialoglycoprotein receptor have thus been described.
However, the synthetic vectors proposed nowadays are still far from performing as well as viral vectors. This may be the consequence in particular of insufficient condensation of the DNA to be transfected and/or difficulties encountered by the

REFERENCES:
patent: 5631237 (1997-05-01), Dzau et al.
Allen et al., FEB Letters, vol. 223, No. 1, pp. 42-46, Oct. 1987.
Dean et al., PNAS, vol. 91, pp. 11762-11766, Nov. 1994.
Farhood et al., Biochimica Et Brophysica Acta, vol. 1111, p. 239-246 (Abstract only), Nov. 1992.
Loeffler et al., Methods in Enzymology, vol. 217 pp. 599-618, 1993.
Boussif et al., PNAS, vol. 92, pp. 7297-7301, Aug. 1995.
Kaneda et al., J. Mol. Med., vol. 73, pp. 289-297, Jun. 1995.

Affiliated with

Also associated with

Rating

Pharmaceutical composition useful for nucleic acid transfection, does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Pharmaceutical composition useful for nucleic acid transfection,, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceutical composition useful for nucleic acid transfection, will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1725974