Year: 2007
Type: other
Abstract: Several different heterologous viral envelope proteins have been evaluated for hepatocyte directed gene transfer including those from Ross River virus (RRV) (37), baculovirus (28;41), and Sendai virus (42).Kang et al. reported a 20 fold improvement in gene transfer efficiency of RRV pseudotyped LV to hepatocytes, as compared to VSVg pseudotyped LV, with detectable gene transfer to liver nonparenchymal cells (37).Although there is one report of a GP64 pseudotyped feline immunodeficiency virus (FIV) LV with hepatocyte specific gene transfer (41), this has not been observed with HIV based LV systems (28) (chapter 3).Sendai virus fusion protein pseudotyped lentiviral vectors displayed preferential hepatocyte gene transfer in vitro, but were not evaluated in vivo, due to problems with incorporation into viral particles and low stability (42).Lentiviral vectors have been evaluated for their therapeutic potential in various animal models of inherited liver disorders.Systemic injection of LVs coding for either human clotting factor VIII or IX has lead to therapeutic levels of protein expression in murine models (36;39;43;44).In immuno-competent animal models, expression levels of the clotting factors were transient and loss of expression correlated with the One disadvantage of a single vector is promoter interference occurring between the TRE promoter and the constitutive promoter used to express tTA or rtTA.To solve this problem, tTA or rtTA was expressed from the TRE promoter resulting in autoregulatory expression.Early attempts at autoregulatory expression of tTA showed toxicity which was believed to be associated with transcriptional squelching Chapter 1 23
Author: David M. Markusic
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1928417058