A novel SV40-based vector successfully transduces and expresses an alpha 1-antitrypsin ribozyme in a human hepatoma-derived cell line

Abstract

Alpha 1-antitrypsin (␣1AT) deficiency disease is one of the ribozyme cleavage. Ribozymes were effective in inhibiting more common hereditary disorders that affects the liver ␣1AT expression in a human hepatoma cell line using a and lung. The liver disease of ␣1AT deficiency is generally newly developed simian virus (SV40) vector system. In thought to be caused by the accumulation of an abnormal addition, the hepatoma cell line was stably transduced with ␣1AT protein in hepatocytes, whereas the lung disease is a modified ␣1AT cDNA that was capable of producing wildthought to be due to a relative lack of the normal protein type ␣1AT protein, but was not cleaved by the ribozyme in the circulation. Therefore, one possible approach to prethat decreased endogenous ␣1AT expression. These vent and treat ␣1AT disease is to both inhibit the results suggest that ribozymes can be employed for the expression of the mutated ␣1AT gene, and to provide a specific inhibition for an abnormal ␣1AT gene product, the means of synthesizing the normal protein. To do this, we first step in designing a gene therapy for the disease. The designed specific hammerhead ribozymes that were capfindings also suggest that the novel SV40-derived vector able of cleaving the ␣1AT mRNA at specific sites, and conmay represent a fundamental improvement in the gene structed a modified ␣1AT cDNA not susceptible to therapeutic armarmentarium.

In vivo post-transcriptional gene silencing of α-1 antitrypsin by adeno-associated virus vectors expressing siRNA

“…One example is the use of a recombinant SV40 vector expressing anti-AAT ribozymes within the liver of the human Z-AAT overexpressing transgenic mouse model. 23 Since augmentation of the wild-type M-AAT can occur from ectopic sites, these downregulation methods within the liver do not have to necessarily be allele-specific. However, it may be necessary to downregulate Z-AAT within a high percentage of hepatocytes to achieve the desired effect.…”

SV40-derived vectors provide effective transgene expression and inhibition of HIV-1 using constitutive, conditional,and pol III promoters

“…2 We and others have observed high efficiency rSV40 transduction of unstimulated PBMC ex vivo, 1,24 and of hepatocytes, neurons and other non-cycling cells in vivo. 1,2,18,[26][27][28] In the current studies, Ͼ95% of SupT1 cells were transduced.…”

HIV-1 proprotein processing as a target for gene therapy

“…Control viruses for these studies have been reported: SV(HBS) and SV(BUGT), which respectively carry the cDNA for hepatitis B surface antigen (HBsAg) and human bilirubin-UDPglucuronosyl-transferase. 44,45 Production of rSV40 derivative virus…”