研究动态
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自我复制RNA的应用。

Applications of self-replicating RNA.

发表日期:2022
作者: Kenneth Lundstrom
来源: International Review of Cell and Molecular Biology

摘要:

自复制RNA病毒载体已被设计用于预防和治疗应用,主要针对传染病和癌症领域。包括阿尔法病毒、黄病毒、麻疹病毒和恙虫病毒在内,利用了正、负链RNA病毒。高水平的RNA扩增提供了病毒表面蛋白和肿瘤抗原的高效表达。动物模型中的免疫接种研究引发了强烈的中和抗体反应。在传染病的背景下,自复制RNA病毒载体的免疫接种已在动物模型中提供了对致命病原体挑战的保护。同样地,接种表达肿瘤抗原的载体也导致了肿瘤的退化和清除,并在动物模型中提供了对肿瘤挑战的保护。病毒RNA的短暂性和非整合性是疫苗开发的理想特性。此外,自复制RNA病毒载体表现出极大的灵活性,因为它们可以应用为重组病毒颗粒、RNA复制子或DNA复制子质粒。特别是在癌症免疫疗法领域进行了几个临床试验。 版权所有 ©2022 Elsevier Inc.。保留所有权利。
Self-replicating RNA viral vectors have been engineered for both prophylactic and therapeutic applications. Mainly the areas of infectious diseases and cancer have been targeted. Both positive and negative strand RNA viruses have been utilized including alphaviruses, flaviviruses, measles viruses and rhabdoviruses. The high-level of RNA amplification has provided efficient expression of viral surface proteins and tumor antigens. Immunization studies in animal models have elicit robust neutralizing antibody responses. In the context of infectious diseases, immunization with self-replicating RNA viral vectors has provided protection against challenges with lethal doses of pathogens in animal models. Similarly, immunization with vectors expressing tumor antigens has resulted in tumor regression and eradication and protection against tumor challenges in animal models. The transient nature and non-integration of viral RNA into the host genome are ideal features for vaccine development. Moreover, self-replicating RNA viral vectors show great flexibility as they can be applied as recombinant viral particles, RNA replicons or DNA replicon plasmids. Several clinical trials have been conducted especially in the area of cancer immunotherapy.Copyright © 2022 Elsevier Inc. All rights reserved.