研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

复合凝胶物作为迄今为止的主要核酸递送载体的最新进展与挑战的全面综述。

Complex Coacervates as a Promising Vehicle for mRNA Delivery: A Comprehensive Review of Recent Advances and Challenges.

发表日期:2023 Aug 10
作者: Chloe Forenzo, Jessica Larsen
来源: MOLECULAR PHARMACEUTICS

摘要:

基于RNA信使(mRNA)的治疗方法在成功应用基于mRNA的COVID-19疫苗之后引起了广泛关注。与传统遗传修饰方法相比,基于mRNA的治疗方法具有多个优点,包括较低的遗传突变风险、短暂和可控的治疗基因表达以及更短的生产时间,这有助于快速应对新兴健康挑战。此外,基于mRNA的治疗方法在治疗癌症、免疫性疾病和神经系统疾病等广泛疾病方面显示出巨大潜力。然而,目前非病毒载体在有效和安全地传递mRNA治疗方法方面存在一些限制,如低封装效率、潜在毒性和有限的稳定性,因此需要探索新策略来克服这些挑战,充分发挥基于mRNA的治疗的潜力。共凝聚物基传递系统最近成为增强mRNA传递的有前景的策略。共凝聚物是由两个或更多大分子聚集形成的,由于能在水环境中形成一个分离的富含大分子的液相,共凝聚物显示出在传递广泛的治疗方法方面的巨大潜力。这种相分离能够使治疗剂被包裹并保护免受降解,并能够实现高效的细胞摄取和控制释放。此外,共凝聚物对mRNA分子的天然亲和性为增强mRNA传递到靶向细胞和组织提供了极好的机会,使共凝聚物基传递系统成为基于mRNA的治疗方法的一个有吸引力的选择。本综述强调了目前mRNA传递策略的限制以及共凝聚物基传递系统的优势,以实现mRNA治疗方法。共凝聚物保护mRNA免受酶降解并增强细胞内摄取,从而实现持久和可控的基因表达。尽管其具有有希望的特性,但共凝聚物作为mRNA传递载体的特定应用尚未得到充分的研究。本综述旨在全面概述共凝聚物介导的mRNA传递,探讨不同共凝聚剂的性质和应用以及通过共凝聚物介导的mRNA封装、释放、稳定性和转化中涉及的挑战和优化策略。通过对最近进展和未来发展方向的综合分析,本综述揭示了共凝聚物介导传递RNA治疗的有前景作用,强调了其在药物传递和基因疗法方面的潜力,为开创性的应用提供了启示。
Messenger RNA (mRNA)-based therapies have gained significant attention, following the successful deployment of mRNA-based COVID-19 vaccines. Compared with traditional methods of genetic modification, mRNA-based therapies offer several advantages, including a lower risk of genetic mutations, temporary and controlled therapeutic gene expression, and a shorter production time, which facilitates rapid responses to emerging health challenges. Moreover, mRNA-based therapies have shown immense potential in treating a wide range of diseases including cancers, immune diseases, and neurological disorders. However, the current limitations of non-viral vectors for efficient and safe delivery of mRNA therapies, such as low encapsulation efficiency, potential toxicity, and limited stability, necessitate the exploration of novel strategies to overcome these challenges and fully realize the potential of mRNA-based therapeutics. Coacervate-based delivery systems have recently emerged as promising strategies for enhancing mRNA delivery. Coacervates, which are formed by the aggregation of two or more macromolecules, have shown great potential in delivering a wide range of therapeutics due to their ability to form a separated macromolecular-rich fluid phase in an aqueous environment. This phase separation enables the entrapment and protection of therapeutic agents from degradation as well as efficient cellular uptake and controlled release. Additionally, the natural affinity of coacervates for mRNA molecules presents an excellent opportunity for enhancing mRNA delivery to targeted cells and tissues, making coacervate-based delivery systems an attractive option for mRNA-based therapies. This review highlights the limitations of current strategies for mRNA delivery and the advantages of coacervate-based delivery systems to enable mRNA therapeutics. Coacervates protect mRNA from enzymatic degradation and enhance cellular uptake, leading to sustained and controlled gene expression. Despite their promising properties, the specific use of coacervates as mRNA delivery vehicles remains underexplored. This review aims to provide a comprehensive overview of coacervate-mediated delivery of mRNA, exploring the properties and applications of different coacervating agents as well as the challenges and optimization strategies involved in mRNA encapsulation, release, stability, and translation via coacervate-mediated delivery. Through a comprehensive analysis of recent advancements and recommended future directions, our review sheds light on the promising role of coacervate-mediated delivery for RNA therapeutics, highlighting its potential to enable groundbreaking applications in drug delivery and gene therapy.