Current Advances in Retroviral Gene Therapy

Abstract

There have been major changes since the incidents of leukemia development in X-SCID patients after the treatments using retroviral gene therapy. Due to the risk of oncogenesis caused by retroviral insertional activation of host genes, most of the efforts focused on the lentiviral therapies. However, a relative clonal dominance was detected in a patient with β-thalassemia Major, two years after the subject received genetically modified hematopoietic stem cells using lentiviral vectors. This disappointing result of the recent clinical trial using lentiviral vector tells us that the current and most advanced vector systems does not have enough safety. In this review, various safety features that have been tried for the retroviral gene therapy are introduced and the possible new ways of improvements are discussed. Additional feature of chromatin insulators, co-transduction of a suicidal gene under the control of an inducible promoter, conditional expression of the transgene only in appropriate target cells, targeted transduction, cell type-specific expression, targeted local administration, splitting of the viral genome, and site specific insertion of retroviral vector are discussed here.

Anticancer Gene Transfer for Cancer Gene Therapy

“…Essentially a harmful cancer-cell characteristic is used to destroy the tumor itself. Retroviruses and Measles viruses have been recently used in cancer-specific retargeting through the use of MMPs (Yi et al, 2011;Cattaneo, 2010). Viral DNA or RNA was manipulated so genes that contained protease recognition sequences were disrupted and fused with linkers containing sequences that are recognized by MMPs.…”

Gene Delivery Systems: Recent Progress in Viral and Non-Viral Therapy

“…In order to enter a host cell, they use the interactions between cellular receptors and virally encoded proteins, which are embedded in the membrane (Hu and Pathak, 2000). Combination of chimeric envelope protein with viral particles allows the retrovirus to bind receptor-positive target cells (Yi et al, 2011). SU in the virion surface binds to CD, which is a cell-surface protein expressed by some T-cells and is found in macrophages.…”

“…Infusion of viral and cellular membranes starts the internalization of the viral nucleus (Yi et al, 2011); the viral envelope combines with the cell membrane. Envelope glycoprotein (Env) of retroviruses is responsible for determining tropism.…”

“…However, one of the disadvantages of current retroviral transfer systems is that they are not specific to types of target cells (Yi et al, 2011).…”

“…This characteristi c p r o p e r t y i s a n advantage for various gene therapy applications used in targeting in post-mitotic and highly differentiated cells. The most important advantage of lentiviruses compared with other retroviruses is their ability for gene transfer to non-dividing cells (Escors and Brecpot, 2010;Yi et al, 2011;Matrai et al, 2009;Freed, 1997). This characteristic is believed to be related to the pathogenic characteristics of lentiviruses, which infect terminally differentiated cells of monocyte/macrophage lineage (Freed, 1997).…”