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Báo cáo y học: " Proviral HIV-genome-wide and pol-gene specific Zinc Finger Nucleases: Usability for targeted HIV gene therapy Misaki Wayengera"

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: " Proviral HIV-genome-wide and pol-gene specific Zinc Finger Nucleases: Usability for targeted HIV gene therapy Misaki Wayengera | Wayengera Theoretical Biology and Medical Modelling 2011 8 26 http www.tbiomed.eom content 8 1 26 THEORETICAL BIOLOGY AND MEDICAL MODELLING RESEARCH Open Access Proviral HIV-genome-wide and pol-gene specific Zinc Finger Nucleases Usability for targeted HIV gene therapy Misaki Wayengera Correspondence wmisaki@yahoo. com Unit of Genetics Genomics Theoretical Biology Dept of Pathology School of Biomedical Science College of Health Sciences Makerere University. P O Box 7072 Kampala Uganda 2 BioMed Central Abstract Background Infection with HIV which culminates in the establishment of a latent proviral reservoir presents formidable challenges for ultimate cure. Building on the hypothesis that ex-vivo or even in-vivo abolition or disruption of HIV-gene genome-action by target mutagenesis or excision can irreversibly abrogate HIV s innate fitness to replicate and survive we previously identified the isoschizomeric bacteria restriction enzymes REases AcsI and ApoI as potent cleavers of the HIV-pol gene 11 and 9 times in HIV-1 and 2 respectively . However both enzymes along with others found to cleave across the entire HIV-1 genome slice SX at palindromic sequences that are prevalent within the human genome and thereby pose the risk of host genome toxicity. A long-term goal in the field of R-M enzymatic therapeutics has thus been to generate synthetic restriction endonucleases with longer recognition sites limited in specificity to HIV. We aimed i to assemble and construct zinc finger arrays and nucleases ZFN with either proviral-HIV-pol gene or proviral-HIV-1 wholegenome specificity respectively and ii to advance a model for pre-clinically testing lentiviral vectors LV that deliver and transduce either ZFN genotype. Methods and Results First we computationally generated the consensus sequences of a 114 dsDNA-binding zinc finger Zif arrays ZFAs or ZifHIV-pol and b two zinc-finger nucleases ZFNs which unlike the AcsI and ApoI homeodomains possess specificity to 18 base-pair