New Vectors for Stable and Safe Gene Modification

摘要: Stable gene modification without affecting normal cellular function is a main goal both for basic and applied science. Current strategies to achieve stable are either very inefficient (homologous recombination) or genotoxic (retroviral transfer). Retroviral vectors derived from oncoretroviruses (murine leukaemia virus MLV) were the first be widely used modifications therapy strategies. They efficient, poorly immunogenic non-pathogenic virus. MLV-based also ones show real therapeutic effect by correcting immune system of about 50 patients with four different severe immunodeficiencies X-linked Severe Combined Immunodeficiency (SCID-X1), SCID-Adenosine Deaminase Deficiency (SCIDADA), Wiskott-Aldrich Syndrome (WAS) Chronic Granulomatous Disease (CGD)(Fischer et al.). However, most applications efficacy incomplete come together serious adverse effects such as cell transformation(Neven al., 2009). Different studies have demonstrated that enhancer elements present in old generation retroviral important transformation(Montini Therefore, safer integrative required replace when required. New expression must consider three aspects: 1efficiency, 2ectopic unregulated transgene 3genotoxicity (genomic alterations due vector integrations). Probably feature reach clinic efficiency. Gene Therapy able efficiently transduce their target cells order benefits. High efficiency especially relevant protein does not confer any positive advantage cells. It therefore keep mind safe no use if minimum. We can say that, at least some applications, longer limitation, safety now concern. The ectopic other aspect take into consideration. As conventional agents, transgenes window where exert function. In many diseases, affected restricted particular tissue, stage development and/or response environmental conditions. non-target well non-physiological levels may cause toxic deleterious effects.