tailieunhanh - Báo cáo y học: "CXCR4 and CCR5 shRNA transgenic CD34+ cell derived macrophages are functionally normal and resist HIV-1 infection"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: "CXCR4 and CCR5 shRNA transgenic CD34+ cell derived macrophages are functionally normal and resist HIV-1 infection | BioMed Central Retrovirology Research Open Access CXCR4 and CCR5 shRNA transgenic CD34 cell derived macrophages are functionally normal and resist HIV-1 infection Joseph Anderson and Ramesh Akkina Address Dept. Microbiology Immunology and Pathology Colorado State University Fort Collins Colorado 80523 USA Email Joseph Anderson - lacrosse@ Ramesh Akkina - akkina@ Corresponding author Published 18 August 2005 Received 20 July 2005 Retrovirology 2005 2 53 doi 1742-4690-2-53 Accepted 18 August 2005 This article is available from http content 2 1 53 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 licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract Background Stable simultaneous knock down of the HIV-1 coreceptors CCR5 and CXCR4 is a promising strategy to protect cells from both R5 macrophage tropic and X4 T cell tropic as well as dual tropic viral infections. The potency of shRNAs in targeted gene silencing qualifies them as powerful tools for long term HIV gene therapy. Our previous work with a bispecific lentiviral vector containing CXCR4 and CCR5 shRNAs showed efficacy in down regulating both coreceptors and conferring viral resistance to both X4 and R5-tropic strains of HIV-1 in cultured cell lines. To extend these results to a stem cell gene therapy setting here we show transduction of primary CD34 hematopoietic progenitor cells to derive normal end stage cells that are resistant to HIV-1 infection. Results The bispecific XHR lentiviral vector harboring CXCR4 and CCR5 shRNA expression cassettes was efficient in transducing CD34 cells. The transduced cells gave rise to morphologically normal transgenic macrophages when cultured in cytokine media. There was a marked down regulation of .