Chemistry: molecular biology and microbiology – Vector – per se
Patent
1995-11-17
1999-04-06
Campell, Bruce R.
Chemistry: molecular biology and microbiology
Vector, per se
4351723, 435 691, 435325, 424 932, 514 44, C12N 701, C12N 1586
Patent
active
058917152
DESCRIPTION:
BRIEF SUMMARY
This application is a national stage application filed under 35 USC 371 of PCT/FR94/00531 filed May 6, 1994.
The present invention relates to new viral vectors, to their preparation and to their use in gene therapy. It also relates to pharmaceutical compositions containing the said viral vectors. More especially, the present invention relates to the use of recombinant adenoviruses of animal origin as vectors for gene therapy.
Gene therapy consists in correcting a deficiency or an abnormality (mutation, aberrant expression, and the like) by introducing genetic information into the cell or organ affected. This genetic information may be introduced either in vitro into a cell extracted from the organ, the modified cell then being reintroduced into the body, or directly in vivo into the appropriate tissue. In this second place, different techniques exist, including various techniques of transfection involving complexes of DNA and DEAE-dextran (Pagano et al., J.Virol. 1 (1967) 891), of DNA and nuclear proteins (Kaneda et al., Science 243 (1989) 375) and of DNA and lipids (Felgner et al., PNAS 84 (1987) 7413), the use of liposomes (Fraley et al., J.Biol.Chem. 255 (1980) 10431), and the like. More recently, the use of viruses as vectors for gene transfer has been seen to be a promising alternative to these physical transfection techniques. In this connection, different viruses have been tested for their capacity to infect certain cell populations. This applies especially to retroviruses (RSV, HMS, MMS, and the like), the HSV virus, adeno-associated viruses and adenoviruses.
Among these viruses, the adenoviruses display certain properties which are advantageous for use in gene therapy. In particular, they have a fairly broad host range, are capable of infecting resting cells and do not integrate in the genome of the infected cell. For these reasons, adenoviruses have already been used for in vivo gene transfer. To this end, different vectors derived from adenoviruses have been prepared, incorporating different genes (.beta.-gal, OTC, .alpha.-1AT, cytokines, and the like). All the vectors derived from the adenoviruses described in the prior art for the purposes of use in gene therapy in humans have hitherto been prepared from adenoviruses of human origin. These appeared, in effect, to be the most suitable for such a use. To limit the risks of multiplication and the formation of infectious particles in vivo, the adenoviruses used are generally modified so as to render them incapable of replication in the infected cell. Thus, the constructions described in the prior art are adenoviruses from which the E1 (E1a and/or E1b) and, where appropriate, E3 regions have been deleted, at the site of which regions sequences of interest are inserted (Levrero et al., Gene 101 (1991) 195; Gosh-Choudhury et al., Gene 50 (1986) 161). However, in addition to this necessary modification step, the vectors described in the prior art retain other drawbacks which limit their exploitation in gene therapy, and in particular risks of recombination with wild-type adenoviruses. The present invention provides an advantageous solution to this problem.
The present invention consists, in effect, in using recombinant adenoviruses of animal origin for gene therapy in humans. The present invention is the outcome of the demonstration that adenoviruses of animal origin are capable of infecting human cells very effectively. The invention is also based on the demonstration that adenoviruses of animal origin are incapable of propagating in the human cells in which they have been tested. Lastly, the invention is based on the surprising discovery that adenoviruses of animal origin are in no way trans-complemented by adenoviruses of human origin, thereby eliminating all risk of recombination and propagation in vivo in the presence of a human adenovirus, capable of leading to the formation of an infectious particle. The vectors of the invention are hence especially advantageous since the risks inherent in the use of viruses as vectors in gene therapy, such as
REFERENCES:
patent: 4920209 (1990-04-01), Davis
Haddada Hedi
Klonjkowski Bernard
Perricaudet Michel
Vigne Emmanuelle
Campell Bruce R.
Priebe Scott D.
Rhone-Poulenc Rorer SA
LandOfFree
Adenoviral vectors of canine origin does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Adenoviral vectors of canine origin, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Adenoviral vectors of canine origin will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1370669