Viral gene delivery

Abstract

Experimental studies of viral gene delivery generally support the principle that virus-mediated gene transfer is indeed possible. However, the field of gene therapy has not yet been realised as a practicable clinical intervention. The delay in translation of laboratory work to clinical utility largely reflects the inability of gene delivery vectors to convey adequate genetic material to a desired location, with adequate durability and low enough toxicity to be effective. Current studies of viral gene therapy vehicles have focused on re-engineering viruses being tested as vectors at present, treating the host to facilitate viral gene transfer and the development of new vectors. Initial enthusiasm for oncoretroviral and adenoviral vectors has cooled, while adeno-associated virus and lentiviral vectors are attracting more interest. Experimental studies with modified SV40-based vectors have also been very promising. The future of gene therapy will probably entail using an array of gene delivery vehicles, each with its own strengths and weaknesses. The vector systems will probably be as diverse as the applications to which they will be put.

Tissue Engineering Tools For Modulation of the Immune Response

“…In selecting among the available vectors, transduction of target cells, duration of gene expression, and vector stability are considerations. The cells that can be targeted may be restricted to whether the vector can transduce dividing and non-dividing cells (38). Cell-specific promoters can be used if the gene delivery needs to be restricted to a single cell type.…”

“…Cell-specific promoters can be used if the gene delivery needs to be restricted to a single cell type. The duration of expression is dependent upon whether the vector integrates into the genome or remains episomal, and also clearance of transduced cells by the immune response (38). The vector's stability impacts the mechanisms by which it can be delivered.…”

“…Innate immune response to the virus results from recognition of the capsid antigens on its surface (38). The resulting inflammatory cytokine secretion may be less than that induced with non-viral vectors (40).…”

Development and Characterization of siRNA Lipoplexes: Effect of Different Lipids, In Vitro Evaluation in Cancerous Cell Lines and In Vivo Toxicity Study

“…Main barriers for the delivery of siRNA are its negative charge and hydrophilicity which hinder its easy diffusion through negatively charged cell membranes and degradation of siRNA by nucleases during blood circulation and after endocytosis ruling out the possibility of use of naked siRNA for better transfection of target cells. Viral vectorbased siRNA delivery has been developed for effective delivery of siRNA inside the cells overcoming the barriers related to the use of naked siRNA (8,9). But this method itself is not devoid of disadvantages.…”

Replication-selective viruses for cancer therapy

“…A third approach is based on methods to diminish the production of an oncogene (e.g., Mdm2) whose expression is aberrantly regulated in tumors [2,3]. Replication-defective viral vectors have been used to allow efficient delivery of a variety of transgenes to target tissues [4,5,6]. However, because these gene delivery vectors cannot discriminate between tumor cells and normal cells they may mainly be useful in local/regional therapy.…”