Adenovirus-mediated gene transfer into striated muscles

Gene transfer to muscle

“…Even with El/E3-deleted adenoviral vectors the capacity for foreign DNA insertion is restricted to about 7.8 kb [20] and hence, for example, cannot accommodate full-length dystrophin cDNAs. Nevertheless, in this case a 6.3 kb human minidystrophin cDNA isolated from one patient with very mild clinical manifestations of Becker MD has been used to construct EUE3-deleted recombinant adenovirus vectors ( [21,22], G. Dickson, unpublished work). In vivo studies involving intramuscular injections into neonatal mdx mice have shown that these adenovirus vectors can efficiently direct the synthesis of a significant amount of the 229 kDa minidystrophin, with 5-50% of fibres showing correct sarcolemmal localization.…”

Gene transfer by viral vectors for gene therapy

“…The inability, however, of retroviral vectors to integrate the viral DNA into the chromosomal DNA of nondividing cells is a difficulty. An additional difficulty in the use of retroviral vectors is the presence of endogenous retroviruses in the human genome at a fairly high copy number (reviewed in [7]), which increases the possibility of the recombination between the retroviral vector and endogenous retrovirus genomes leading to the generation of infectious virus recombinants. It has been shown [1] that the virus progeny of vector-producing cell lines must be carefully tested for replication-competent retroviruses.…”

“…Acsadi et al [7] took advantage of the adenovirus genome which contains large portions of the viral DNA that can be substituted with foreign genes. Adenoviruses have not been reported to be associated with human cancers, and adenovirus recombinants are stable.…”

“…This technique has advantages and disadvantages. In the forthcoming volume Gene Transfer by Viral Vectors for Gene Therapy [2] we plan to provide a forum for the analysis of developments in the construction and use of viral vectors useful for gene therapy [3][4][5][6][7].…”

Strategy for Treating Motor Neuron Diseases Using a Fusion Protein of Botulinum Toxin Binding Domain and Streptavidin for Viral Vector Access: Work in Progress

“…Direct injection of substances or cells into the spinal cord [41], infusions into the spinal fluid [14], and extensive injections of viral vectors throughout skeletal muscles [33] are possible but difficult methods of delivering agents or transferring genes to motor neurons. However, it has been shown that certain viral vectors (Adenovirus, AAV, and lentivirus) do undergo retrograde transport, provided that they enter the motor nerve terminals [33,42]. For the most part, this is relatively inefficient, because only a small proportion of the viral vectors injected into the large bulk of the skeletal muscle can reach the very small region of the motor nerve terminals.…”