RNA interference for improving the outcome of islet transplantation

被引:28
作者
Li, Feng [1 ]
Mahato, Ram I. [1 ]
机构
[1] Univ Tennessee, Hlth Sci Ctr, Dept Pharmaceut Sci, Memphis, TN 38103 USA
基金
美国国家卫生研究院;
关键词
RNA interference; Islet transplantation; siRNA; shRNA; ENDOTHELIAL GROWTH-FACTOR; SHORT-HAIRPIN RNA; POLY(ETHYLENE GLYCOL)-SIRNA CONJUGATE; POLYELECTROLYTE COMPLEX MICELLES; DENDRITIC CELL MATURATION; FACTOR GENE DELIVERY; DOUBLE-STRANDED-RNA; IN-VIVO DELIVERY; BETA-CELL; SIRNA DELIVERY;
D O I
10.1016/j.addr.2010.11.003
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Islet transplantation has the potential to cure type 1 diabetes. Despite recent therapeutic success, it is still not common because a large number of transplanted islets get damaged by multiple challenges including instant blood mediated inflammatory reaction, hypoxia/reperfusion injury, inflammatory cytokines, and immune rejection. RNA interference (RNAi) is a novel strategy to selectively degrade target mRNA. The use of RNAi technologies to downregulate the expression of harmful genes has the potential to improve the outcome of islet transplantation. The aim of this review is to gain a thorough understanding of biological obstacles to islet transplantation and discuss how to overcome these barriers using different RNAi technologies. This eventually will help improve islet survival and function post transplantation. Chemically synthesized small interferring RNA (siRNA), vector based short hairpin RNA (shRNA), and their critical design elements (such as sequences, promoters, and backbone) are discussed. The application of combinatorial RNAi in islet transplantation is also discussed. Last but not the least, several delivery strategies for enhanced gene silencing are discussed, including chemical modification of siRNA, complex formation, bioconjugation, and viral vectors. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:47 / 68
页数:22
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