Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing compound containing saccharide radical
Patent
1998-04-20
2000-02-01
Guzo, David
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing compound containing saccharide radical
4353201, 4352351, 435455, 435456, 435366, 435371, 435372, C12N 1564, C12N 1586, C12N 510
Patent
active
06020172&
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to methods for gene therapy in humans using novel ovine adenoviral vectors. In particular, the present invention is directed to methods of introducing genes into human cells such that the genes are functionally expressed by the cells.
BACKGROUND ART
Genetic defects which cause diseases such as cancer, cystic fibrosis, muscular dystrophy and many other disorders contribute greatly to the cost of human health care. Consequently, there are major research efforts worldwide to develop new approaches to provide genetic therapy effective at the level of the somatic cell.
Central to this work are a variety of gene vectors derived from viruses such as retro-, pox, adeno-associated and adenoviruses. The viruses from which these vectors are derived are of low pathogenicity and the vectors are designed to carry therapeutic genes into the host cell. Under appropriate conditions these may produce products which can vaccinate the host, change cell phenotypes, stimulate immune responses, supplement genetic defects or lead to cell death.
No single viral vector has all the attributes desirable for all therapeutic situations. Some vectors are better suited to particular tasks than others because of their biological properties. For example, as retroviruses can integrate into the host genome, these vectors appear to be well suited to deliver genes to dividing cells such as the stem cells of the haemopoietic cell lineage. In contrast, adenovirus vectors do not usually integrate their DNA but are able to efficiently infect non-dividing cells. Human adenoviral vectors have been used to deliver genes to a variety of tissues in humans and in animal models, eg, lungs, muscle, liver, vascular and brain cells. A major disadvantage of the use of human adenoviruses is that as these viruses naturally infect humans, it can often be the case that the person to be treated with the human adenoviral vector has circulating antibodies which can neutralise the vector prior to it reaching the target cell. Immunity also results in efficient clearance of the virus from the host by the cellular immune system, thereby rapidly diminishing any therapeutic effect due to gene expression. Thus, there is a need to develop vectors derived from viruses that normally do not infect humans, so as to overcome the problem of pre-existing immunity. As ovine and human adenoviruses are serologically distinct, the use of an ovine adenovirus (OAV) as a vector may achieve this objective. It is also essential to develop vectors whose presence in the host is disguised so that the immune response is less severe and gene expression is more likely to persist. As ovine adenovirus does not replicate productively, even in most non-ovine animal cells (1) it was expected to replicate abortively in human cells, provided that it could infect them. A block in replication at all early step would lead to minimal expression of viral products in the infected cell, with a consequent low level induction of the cellular immune response.
The present inventors have developed an adenoviral vector derived from ovine adenovirus OAV287. The virus and viral vectors derived therefrom are fully described in International Patent Application Number WO 96/03508 filed on Jul. 26, 1995 in the name of Commonwealth Scientific and Industrial Research Organisation (hereinafter referred to as "the PCT Application" and incorporated herein by reference). The adenoviral vector disclosed in the PCT Application was found to be suitable for use as a vector to introduce foreign DNA into a variety of non-human cells, and in particular into sheep cells. The genome sequence and arrangement of OAV287 is different from all known human, animal and avian adenoviruses, including the canine adenovirus described in International Patent Application Numbers WO 91/11525 and WO 94/26914, the bovine adenovirus described in International Patent Application Number WO 95/16048 and the avian CELO isolate (2). OAV is also serotypically distinct (1) and is not neutralised by serum huma
REFERENCES:
Chen et al., PNAS, vol. 94, pp. 1645-1650, Mar. 1997.
Verma et al., Nature, vol. 389, pp. 239-242, Sep. 18. 1997.
Orkin et al., "Report and Recommendations of the Panel to Assess the NIH Investment in Research on Gene Therapy", Dec. 7, 1995.
Vrati et al., "Sequence of Ovine Adenovirus Homologs for 100K Hexon Assembly, 33K, pVIII, and Fibre Genes: Early Region E3 is Not in the Expected Location", Virology, vol. 209, Jun. 1, 1995, pp. 400-408.
Vrati et al., "Construction and Transfection of Ovine, adenovirus Genomic Clones to Rescue Modified Viruses", pp. 200-203.
Vrati et al., "Unique Genome Arrangements of an Ovine Adenovirus: Identification of New Proteins and Proteinase Cleavage Sites", (1996), pp. 86-199.
Lemarchand et al., "In Vivo Gene Transfer and Expression in Normal Uninjured Blood Vessels using replication-Deficient Recombinant Adenovirus", pp. 1132-1138.
Boyle David B. et al., "Characterisation of Australian ovine adenovirus isolates", Veterinary Microbiology, vol. 41, No. 3, 1994, pp. 281-291.
Stevenson, Susan C. et al, "Human Adenovirus Serotypes 3 and 5 Bind to Two Different Cellular Receptors via the Fiber Head Domain", Journal of Virology, May 1995, vol. 69, No. 5, pp. 2850-2857.
Taneja, Samir S. et al., "In vitro target specific gene therapy for prostate cancer utilizing a prostate specific antigen promoter-driven adenoviral vector", Proceedings of the American Association for Cancer Research, vol. 35, Mar. 1994, pp. 375, abstract #2236.
Commonwealth Scientific and Industrial Research Organisation
Guzo David
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