ABSTRACT

Introduction: Gene therapy is a breakthrough medical field which focuses on the therapeutic delivery of recombinant nucleic acids in order to treat or prevent a broad spectrum of diseases. However, a number of important obstacles remain before its wide introduction into clinical practice can be envisaged. One of the biggest bottlenecks is the lack of efficient and safe delivery technologies, particularly, for in vivo distribution. Above and beyond standard requirements for carriers, the delivery systems for gene therapy ideally use a hit-and-run principle (to minimize off-target effect and display of immunogenic moieties). None of the currently used viral vectors fulfills all of these requirements. Therefore, the growing variety of non-viral delivery platforms represents a promising alternative.

Areas covered: This review summarizes the Layer-by-Layer (LbL) approaches that can be effectively used for the gene delivery, considering various examples with the transfer of pDNA, mRNA, siRNA as well as genome-editing tools. Ex vivo gene modification of clinically relevant cells and clinical aspects for possible application of LbL systems in gene therapy are also underlined.

Expert opinion: The LbL technique provides broad opportunities for the delivery of genetic material for various purposes and offers promise for future clinical application in gene therapy.

摘要

简介：基因治疗是一个突破性的医学领域，专注于重组核酸的治疗性传递，以治疗或预防广泛的疾病。然而，在将其广泛引入临床实践之前，仍然存在许多重要障碍。最大的瓶颈之一是缺乏高效和安全的递送技术，尤其是体内分配技术。除了对载体的标准要求之外，基因治疗的递送系统理想地使用命中和运行原理（以最小化脱靶效应和免疫原性部分的展示）。目前使用的病毒载体都不能满足所有这些要求。因此，越来越多的非病毒递送平台代表了一种有前途的替代方案。

涵盖的领域：本综述总结了可有效用于基因传递的逐层 (LbL) 方法，考虑了 pDNA、mRNA、siRNA 以及基因组编辑工具转移的各种示例。还强调了临床相关细胞的离体基因修饰和 LbL 系统在基因治疗中可能应用的临床方面。

专家意见：LbL 技术为各种用途的遗传物质提供了广泛的机会，并为基因治疗的未来临床应用提供了希望。