Abstract: Gene therapy is a promising approach for the treatment of several diseases, such as chronic or viral infections, inherited disorders, and cancer. The cellular internalization of exogenous nucleic acids (NA) requires efficient delivery vehicles to overcome their inherent pharmacokinetic drawbacks, e.g. electrostatic repulsions, enzymatic degradation, limited cellular uptake, fast clearance, etc. Nanotechnological advancements have enabled the use of polymer-based nanostructured biomaterials as safe and effective gene delivery systems, in addition to viral vector delivery methods. Among the plethora of polymeric nanoparticles (NPs), this review will provide a comprehensive and in-depth summary of the polyester-based nanovehicles, including poly(lactic-co-glycolic acid) (PLGA) and polylactic acid (PLA) NPs, used to deliver a variety of foreign NA, e.g. short interfering RNA (siRNA), messenger RNA (mRNA), and plasmid DNA (pDNA). The article will review the versatility of polyester-based nanocarriers including their recent application in the delivery of the clustered, regularly‐interspaced, short palindromic repeats/Cas (CRISPR/Cas) genome editing system for treating gene-related diseases. The remaining challenges and future trend of the targeted delivery of this revolutionary genome-editing system will be discussed. Special attention will be given to the pivotal role of nanotechnology in tackling emerging infections such as coronavirus disease 2019 (COVID-19): ground-breaking mRNA vaccines delivered by NPs are currently used worldwide to fight the pandemic, pushing the boundaries of gene therapy.

Keywords: PLGA, PLA, siRNA, CRISPR, COVID-19, CLAN


中文翻译：

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聚酯纳米粒子介导的基因传递的最新进展和挑战

摘要：基因治疗是治疗多种疾病的一种有前途的方法，例如慢性或病毒感染、遗传性疾病和癌症。外源核酸（NA）的细胞内化需要有效的递送载体来克服其固有的药代动力学缺点，例如静电排斥、酶促降解、有限的细胞摄取、快速清除等。纳米技术的进步使得基于聚合物的纳米结构生物材料成为可能除了病毒载体传递方法之外，还包括安全有效的基因传递系统。在众多的聚合物纳米颗粒（NP）中，本综述将对聚酯基纳米载体进行全面而深入的总结，包括聚乳酸-乙醇酸共聚物（PLGA）和聚乳酸（PLA）纳米颗粒，用于递送多种外源 NA，例如短干扰 RNA (siRNA)、信使 RNA (mRNA) 和质粒 DNA (pDNA)。本文将回顾聚酯纳米载体的多功能性，包括它们最近在用于治疗基因相关疾病的成簇、规则间隔、短回文重复序列/Cas (CRISPR/Cas) 基因组编辑系统中的应用。将讨论这一革命性基因组编辑系统的靶向递送的剩余挑战和未来趋势。将特别关注纳米技术在应对 2019 年冠状病毒病 (COVID-19) 等新出现的感染方面的关键作用：纳米颗粒提供的突破性 mRNA 疫苗目前在全球范围内用于抗击这一流行病，突破了基因治疗的界限。

关键词： PLGA、PLA、siRNA、CRISPR、COVID-19、CLAN