tailieunhanh - Báo cáo y học: "Allele dependent silencing of COL1A2 using small interfering RNAs"

Tuyển tập các báo cáo nghiên cứu khoa học ngành y học tạp chí Medical Sciences dành cho các bạn sinh viên ngành y tham khảo đề tài: Allele dependent silencing of COL1A2 using small interfering RNAs. | Int. J. Med. Sci. 2008 5 361 International Journal of Medical Sciences ISSN 1449-1907 2008 5 6 361-365 Ivyspring International Publisher. All rights reserved Research Paper Allele dependent silencing of COL1A2 using small interfering RNAs Katarina Lindahl Carl-Johan Rubin Andreas Kindmark Osten Ljunggren H Dept. of Medical Sciences Uppsala University Uppsala Sweden. H Correspondence to Osten Ljunggren Department of Medical Sciences Uppsala University Hospital SE-751 85 Uppsala Sweden. Tel 018-611 49 06 Fax 018-55 36 01 E-mail Received Accepted Published Osteogenesis imperfecta OI is generally caused by a dominant mutation in Collagen I encoded by the genes COL1A1 and COL1A2. To date there is no satisfactory therapy for OI but inactivation of the mutant allele through small interfering RNAs siRNA is a promising approach as siRNAs targeting each allele of a polymorphism could be used for allele-specific silencing irrespective of the location of the actual mutations. In this study we examined the allele dependent effects of several tiled siRNAs targeting a region surrounding an exonic COL1A2 T C polymorphism rs1800222 in heterozygous primary human bone cells. Relative abundances of COL1A2 alleles were determined by cDNA sequencing and overall COL1A2 abundance was analyzed by quantitative PCR. One of the siRNAs decreased overall COL1A2 abundance by 71 of which 75 was due to silencing of the targeted T-allele. In conclusion allele-preferential silencing of Collagen type I genes may be a future therapeutic approach for OI. Key words COL1A2 allele-preferential silencing Osteogenesis imperfecta INTRODUCTION Osteogenesis imperfecta OI is a heterogeneous disease of the connective tissue with an incidence of approximately 1 10 000. The principal sign of OI is fragile bones with multiple fractures but the disease can affect many other tissues as well. The mildest form of OI type I is often due to a .