基于信使RNA(mRNA)的疗法获得了极大的关注,在成功部署基于mRNA的COVID-19疫苗之后。与传统的基因改造方法相比,基于mRNA的疗法提供了几个优点,包括降低基因突变的风险,临时和受控的治疗基因表达,和更短的生产时间,这有助于对新出现的健康挑战做出快速反应。此外,基于mRNA的疗法在治疗包括癌症在内的多种疾病方面显示出巨大的潜力。免疫性疾病,和神经系统疾病。然而,目前非病毒载体对mRNA治疗的有效和安全递送的局限性,如封装效率低,潜在毒性,和有限的稳定性,有必要探索新的策略来克服这些挑战并充分实现基于mRNA的疗法的潜力。基于凝聚层的递送系统最近已经成为增强mRNA递送的有希望的策略。凝聚层,它们是由两个或多个大分子聚集形成的,由于它们能够在水性环境中形成分离的富含大分子的流体相,因此在递送广泛的治疗剂方面显示出巨大的潜力。这种相分离能够捕获和保护治疗剂免于降解以及有效的细胞摄取和受控释放。此外,凝聚层对mRNA分子的天然亲和力为增强mRNA向靶细胞和组织的递送提供了极好的机会,使基于凝聚层的递送系统成为基于mRNA的治疗的有吸引力的选择。这篇综述强调了当前mRNA递送策略的局限性以及基于凝聚层的递送系统实现mRNA治疗的优势。凝聚层保护mRNA免受酶降解并增强细胞摄取,导致持续和受控的基因表达。尽管它们有前途的特性,凝聚物作为mRNA递送载体的具体用途仍未得到充分开发。这篇综述旨在提供凝聚层介导的mRNA递送的全面概述。探索不同凝聚剂的性质和应用,以及mRNA封装中的挑战和优化策略,释放,稳定性,和通过凝聚体介导的传递进行翻译。通过对最新进展和建议的未来方向的全面分析,我们的综述阐明了凝聚层介导的递送在RNA治疗中的有希望的作用,强调其在药物递送和基因治疗中具有突破性应用的潜力。
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.