Engineering antibody-like inhibitors to prevent and treat HIV-1 infection.
Engineering antibody-like inhibitors to prevent and treat HIV-1 infection.
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DOI：
10.1097/coh.0000000000000367
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发表时间：
2017-05
影响因子：
4.1
通讯作者：
Farzan M
中科院分区：
文献类型：
--
作者：
Gardner MR;Farzan M
在这里，我们讨论最近开发的HIV-1进入抑制剂，它可以靶向HIV-1包膜糖蛋白(Env)上的多个表位，重点是eCD4-Ig。其中一些抑制剂比迄今为止任何一种抗体都更有效、范围更广。我们还讨论了使用重组腺相关病毒(RAAV)载体作为长期表达这些抑制物的平台。HIV-1Env的大部分外部可被广谱中和抗体(BNAbs)靶向。最近的研究结合了来自不同bNAb的可变区或Fabs，通常与受体模拟成分相结合，创造出广泛、有效和难以逃脱的抑制剂。RAAV载体可以在体内表达这些抑制物多年，突出了它们预防或治疗HIV-1感染的能力。通过靶向Env上的多个表位，双特异性和抗体样抑制物可以比bNAbs更广泛和更有效。如果这些抑制剂由递送平台(如rAAV载体)给药，但只有在解决了rAAV限制之后，它们才能提供长期保护，甚至抑制HIV-1。
Here we discuss recently developed HIV-1 entry inhibitors that can target multiple epitopes on the HIV-1 envelope glycoprotein (Env), with an emphasis on eCD4-Ig. Some of these inhibitors are more potent and broader than any single antibody characterized to date. We also discuss the use of recombinant adeno-associated virus (rAAV) vectors as a platform for long-term expression of these inhibitors. Much of the exterior of HIV-1 Env can be targeted by broadly neutralizing antibodies (bNAbs). Recent studies combine the variable regions or Fabs from different bNAbs, often with the receptor-mimetic components, to create broad, potent, and hard-to-escape inhibitors. rAAV vectors can express these inhibitors for years in vivo, highlighting their ability to prevent or treat HIV-1 infection. By targeting multiple epitopes on Env, bispecific and antibody-like inhibitors can be broader and more potent than bNAbs. These inhibitors can provide long-term protection from, and perhaps suppression of, HIV-1 if they are administered by a delivery platform, like rAAV vectors, but only after rAAV limitations are addressed.