TAILIEUCHUNG - Báo cáo y học: "Characterization of human adenovirus 35 and derivation of complex vectors"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Characterization of human adenovirus 35 and derivation of complex vectors | McVey et al. Virology Journal 2010 7 276 http content 7 1 276 VIROLOGY JOURNAL RESEARCH Open Access Characterization of human adenovirus 35 and derivation of complex vectors 11 1 11 Duncan McVey Mohammed Zuber Damodar EttyReddy Christopher D Reiter Douglas E Brough Gary J Nabel2 C Richter King1 3 Jason G D Gall1 Abstract Background Replication-deficient recombinant adenoviral vectors based on human serotype 35 Ad35 are desirable due to the relatively low prevalence of neutralizing antibodies in the human population. The structure of the viral genome and life cycle of Ad35 differs from the better characterized Ad5 and these differences require differences in the strategies for the generation of vectors for gene delivery. Results Sequences essential for E1 and E4 function were identified and removed and the effects of the deletions on viral gene transcription were determined. In addition the non-essential E3 region was deleted from rAd35 vectors and a sequence was found that did not have an effect on viability but reduced viral fitness. The packaging capacity of rAd35 was dependent on pIX and vectors were generated with stable genome sizes of up to 104 of the wild type genome size. These data were used to make an E1- E3- E4-deleted rAd35 vector. This rAd35 vector with multiple gene deletions has the advantages of multiple blocks to viral replication . E1 and E4 deletions and a transgene packaging capacity of Kb comparable to rAd5 vectors. Conclusions The results reported here allow the generation of larger capacity rAd35 vectors and will guide the derivation of adenovirus vectors from other serotypes. Introduction Recombinant adenovirus rAd -based gene transfer vectors are currently under investigation in a variety of gene therapy and vaccine clinical trials. There are more than 370 such clinical trials that are ongoing for broad applications including infectious diseases and cancer therapy http legacy wileychi genmed clinical .

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