What they are, How they Work and Why they do What they do? The Story of SV40-derived Gene Therapy Vectors and What They Have to Offer

Abstract

The natural function of viruses is to deliver their genetic material to cells. Among the most effective of viruses in doing that is Simian Virus-40 (SV40). The properties that make SV40 a successful virus make it an attractive candidate for use as a gene delivery vehicle: high titer replication, infectivity for almost all nucleated cell types whether the cells are dividing or resting, potential for integration into cellular DNA, a peculiar pathway for entering cells that bypasses the cells' antigen processing apparatus, very high stability, and the apparent ability to activate expression of its own capsid genes in trans. Exploiting these and other characteristics of wild type (wt) SV40, increasing numbers of laboratories are studying recombinant (r) SV40-derived vectors. Among the uses to which these vectors have been applied are: delivering therapy to inhibit HIV, hepatitis C virus (HCV) and other viruses; correction of inherited hepatic and other protein deficiencies; immunizing against lentiviral and other antigens; treatment of inherited and acquired diseases of the central nervous system; protecting the lung and other organs from free radical-induced injury; and many others. The effectiveness of these vectors is a reflection of the adaptive evolution that produced their parent virus, wt SV40. This article explores how and why these vectors work, their strengths and their limitations, and provides a functional model for their exploitation for experimental and clinical applications.

Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

“…There are reports that recombinant SV40 vectors and in vitro assembled SV40 virus-like particles are capable of efficiently transducing many mammalian cell types (Kimchi-Sarfaty et al, 2004; Lund et al, 2005; Strayer et al, 2005). However, by using quantitative measures of early viral gene expression, we found considerable differences in the ability of different cells to be infected by SV40 and SV40-based vectors generated in permissive monkey cells.…”

Antioxidant enzyme gene delivery to protect from HIV-1 gp120-induced neuronal apoptosis

“…We used rSV40s here since they are excellent delivery vehicles for neurons, both in vivo and in vitro. 59,[62][63][64] As a result of their transduction efficiency and effectiveness in mitigating gp120-induced apoptosis, these vectors may serve as investigative tools to elucidate mechanisms of neuron damage in HIV infection of CNS. Thus, detoxification of ROS by SV(GPx1) or SV(SOD1) protects from HIVinduced apoptosis and may serve as a potential gene therapy strategy for people with HIV encephalopathy.…”

Replication-deficient rSV40 mediate pancreatic gene transfer and long-term inhibition of tumor growth

“…13 SV40-derived, tag deleted vectors are replication incompetent and deliver stable transgene expression with high efficiency to unselected cells of many different lineages, in vitro and in vivo. 13 These vectors can be easily prepared without helper viruses, and concentrated to high titer following purification (10 12 infectious units/ml).…”

“…13 SV40-derived, tag deleted vectors are replication incompetent and deliver stable transgene expression with high efficiency to unselected cells of many different lineages, in vitro and in vivo. 13 These vectors can be easily prepared without helper viruses, and concentrated to high titer following purification (10 12 infectious units/ml). 13 We thus tested whether SV40 vectors could transduce human pancreatic cancer cells, maintain transgene expression without selection throughout in vitro cell culture, and slow pancreatic tumor progression in vivo.…”

“…13 These vectors can be easily prepared without helper viruses, and concentrated to high titer following purification (10 12 infectious units/ml). 13 We thus tested whether SV40 vectors could transduce human pancreatic cancer cells, maintain transgene expression without selection throughout in vitro cell culture, and slow pancreatic tumor progression in vivo.…”