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Báo cáo y học: " HIV-1 resistance conferred by siRNA cosuppression of CXCR4 and CCR5 coreceptors by a bispecific lentiviral vector"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: HIV-1 resistance conferred by siRNA cosuppression of CXCR4 and CCR5 coreceptors by a bispecific lentiviral vector. | AIDS Research and Therapy BioMed Central Research Open Access HIV-I resistance conferred by siRNA cosuppression of CXCR4 and CCR5 coreceptors by a bispecific lentiviral vector Joseph Anderson and Ramesh Akkina Address Dept Microbiology Immunology and Pathology Colorado State University Fort Collins Colorado 80523 USA Email Joseph Anderson - lacrosse@colostate.edu Ramesh Akkina - akkina@colostate.edu Corresponding author Published 13 January 2005 Received 26 October 2004 AIDS Research and Therapy 2005 2 1 doi 10.1186 1742-6405-2-1 Accepted 13 January 2005 This article is available from http www.aidsrestherapy.cOm content 2 1 1 2005 Anderson and Akkina licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http creativecommons.org licenses by 2.0 which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract Background RNA interference RNAi mediated by small interfering RNAs siRNAs has proved to be a highly effective gene silencing mechanism with great potential for HIV AIDS gene therapy. Previous work with siRNAs against cellular coreceptors CXCR4 and CCR5 had shown that down regulation of these surface molecules could prevent HIV-1 entry and confer viral resistance. Since monospecific siRNAs targeting individual coreceptors are inadequate in protecting against both T cell tropic X4 and monocyte tropic R5 viral strains simultaneously bispecific constructs with dual specificity are required. For effective long range therapy the bispecific constructs need to be stably transduced into HIV-1 target cells via integrating viral vectors. Results To achieve this goal lentiviral vectors incorporating both CXCR4 and CCR5 siRNAs of short hairpin design were constructed. The CXCR4 siRNA was driven by a U6 promoter whereas the CCR5 siRNA was driven by an H1 promoter. A CMV promoter driven EGFP reporter gene is also incorporated in the .