期刊
ADVANCED MATERIALS
卷 34, 期 10, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202107852
关键词
antigenicity; immunogenicity; PEG; RNA aptamers; RNA therapeutics
类别
资金
- National Institutes of Health [R41HL139234-01]
RNA aptamers are a promising class of therapeutics, but their poor blood circulation has limited their clinical potential. In this study, researchers address this limitation by conjugating RNA aptamers with a next-generation PEG-like brush polymer. The conjugate retains the therapeutic action of the drug and can be easily reversed, while avoiding the reactivity of pre-existing PEG antibodies. These findings have important implications for rescuing the PEGylation of RNA therapeutics and vaccines from the adverse effects of PEG.
Ribonucleic acid (RNA) therapeutics are an emerging class of drugs. RNA aptamers are of significant therapeutic and clinical interest because their activity can be easily reversed in vivo-a useful feature that is difficult to achieve using other therapeutic modalities. Despite their therapeutic promise, RNA aptamers are limited by their poor blood circulation. The attachment of polyethylene glycol (PEG) to RNA aptamers addresses this limitation. However, an RNA aptamer-PEG conjugate that is a reversible anticoagulant fails in a clinical trial due to the reactivity of the conjugate with pre-existing PEG antibodies and has cast a pall over PEGylation of aptamers and other biologics, despite its long history of utility in drug delivery. Here, PEG antibody-reactivity of this RNA aptamer is eliminated by conjugating it to a next-generation PEG-like brush polymer-poly[(oligoethylene glycol) methyl ether methacrylate)] (POEGMA). The conjugate retained the drug's therapeutic action and the ability to be easily reversed. Importantly, this conjugate does not bind pre-existing PEG antibodies that are prevalent in humans and does not induce a humoral immune response against the polymer itself in mice. These findings suggest a path to rescuing the PEGylation of RNA therapeutics and vaccines from the deleterious side-effects of PEG.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据