A capsid-modified adenovirus vector devoid of all viral genes: assessment of transduction and toxicity in human hematopoietic cells

摘要: Inefficient gene transfer has limited the success of therapy in hematopoietic system. Here we develop a novel chimeric adenovirus (Ad) vector containing Ad serotype 11 fiber-modified capsids and E1/E3 deleted viral genomes (Ad5/11) or devoid all genes (ΔAd5/11). The capsid-modified vectors transduced human cells more efficiently than unmodified Ad5-based vector. absence from ΔAd5/11 allowed for transduction without associated toxicity seen with first-generation Chimeric were used transient expression ecotropic retrovirus receptor (ecoR) Mo7e (a CD34-positive, c-Kit-positive, growth-factor-dependent cell line) as model progenitor cells. Expression ecoR conferred susceptibility to subsequent retroviral transduction. express expansion retrovirally cells, whereas Ad5/11 resulted cytotoxicity and, over time, loss expressing retrovirus-vector-derived transgene.