Replication-deficient vectors, gene therapy

Other types of replication-deficient viral vectors that have been used in the gene therapy field include Herpes simplex viral (HSV) vectors that (1) are able to transduce nondividing cells and (2) are highly infective for neurologic tissue and vaccinia vectors. Vaccinia vectors in turn (1) are able to transduce nondividing cells and (2) have the ability to efficiently infect many types of cells. The primary safety concerns for HSV vectors are the potential for tropism to the CNS and the potential for latency and reactivation. Vaccinia vectors contain the same backbone as the smallpox vaccine, thus the available safety databases for vaccinia administration in humans consist primarily of preventive vaccination in a healthy population. Principal safety concerns with the use of vaccinia vectors include (1) their ability to replicate in humans and possibly... 

Fig. 6.5. Use of helper cell lines in the production of replication-deficient retroviral vectors for gene therapy.

Wiknott, R.W. and Whitsett, J., A phase 1 study of gene therapy of cystic fibrosis utilizing a replication deficient recombinant adenovirus vector to deliver the human cystic fibrosis trans-membrane conductance regulator cDNA to the airways. Bethesda, MD, Office of Recombinant DNA Activity, NIH. 

Other viral vectors have also been developed for use in gene therapy. These include the herpes simplex virus, the vaccinia virus and Sinbis virus. However, these vectors have not been widely studied and it is not clear what advantages they may hold over retroviral, adenoviral or AAV vectors. Recently, limited-replicating viral vectors, such as the Onyx-015 virus, have been developed. The Onyx virus is an ElB deleted adenovirus that can only replicate in p53 deficient cells advantage ofthese vectors is that their replication is limited mainly to tumour cells and that permitting the replication of the virus produces more efficient transfection of the tumour cells. Studies are ongoing to demonstrate the usefulness and safety of replicating vectors. 

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