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Genetic modification of pigs for solid organ xenotransplantation9 z4 ^# S" B2 q3 R
异种器官为目的的转基因猪
) C# {6 A, ?# ?' u/ s; c/ J; E原文来自于http://www.transplantationreviews.com/article/S0955-470X(10)00071-6/abstract
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摘要:小型猪被广泛认为是人类异种实质性器官移植最合适的供体,而要想将其应用于临床,一定要对猪进行基因修饰。对异种移植障碍的研究认识让我们意识到要通过提高基因操作技术来解决这些问题。现在已经能够通过过表达补体调节因子或者定点敲除合成主要异种抗原糖的酶来克服超急性排斥反应。接下来的无序凝血障碍、诱导抗体、细胞介导的排斥反应仍然是存在的挑战。现在这些不兼容反应的机制已经被弄清楚,研究者正着手于多基因修饰来解决这些问题。另外,新技术的出现帮助我们及时地产生相当多的基因修饰猪。这篇文章本文追溯了转基因猪用于异种器官移植的基础和前期工作,这些工作推进了其向临床应用的迈进。) P( a( u6 h/ W9 v4 c9 i; o6 l/ w
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Xenotransplantation of solid organs will only ever become a clinical reality with genetic modification of the pig, which is now widely1 h) t& {; e2 k7 U* B$ z, E
accepted as the most likely donor species for humans. The understanding of the barriers to xenotransplantation has required advances in* _ u( }! W q% E+ [3 j+ v
genetic technologies to resolve these problems. Hyperacute rejection has been overcome by overexpression of complement regulatory
[, l6 J. J( C; p, F+ ]proteins or targeted disruption of the enzyme associated with the major carbohydrate xenoantigen. The subsequent barriers of disordered
7 b, M% y9 c/ i" q: ucoagulation, induced antibody, and cell-mediated rejection remain challenging. The mechanisms for these incompatibilities are being+ w: r- Z% P# H
deciphered, and multiple genetic manipulations to resolve these issues are currently in progress. Moreover, new technologies offer help to
6 g7 `4 {) t( r% H9 Uproducing sizeable numbers of modified pigs in a timely manner. This article retraces the basis and foreshadows progress of the genetically
1 Q. B* u- U( W+ {& c0 W/ Kmodified pig for xenotransplantation as it advances toward the clinic.
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个人理解,多多指点……# }2 o9 H0 C& H9 d- \
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