To realize the full potential of emerging nucleic acid therapies, there is a need for effective delivery agents to transport cargo to cells of interest. Protein materials exhibit several unique properties, including biodegradability, biocompatibility, ease of functionalization via recombinant and chemical modifications, among other features, which establish a promising basis for therapeutic nucleic acid delivery systems. In this review, we highlight progress made in the use of non-viral protein-based nanoparticles for nucleic acid delivery in vitro and in vivo, while elaborating on key physicochemical properties that have enabled the use of these materials for nanoparticle formulation and drug delivery. To conclude, we comment on the prospects and unresolved challenges associated with the translation of protein-based nucleic acid delivery systems for therapeutic applications.

为了充分发挥新兴核酸疗法的潜力，需要有效的递送剂将货物运输到感兴趣的细胞。蛋白质材料表现出多种独特的特性，包括生物降解性、生物相容性、易于通过重组和化学修饰实现功能化等特性，这些特性为治疗性核酸递送系统奠定了有前景的基础。在这篇综述中，我们重点介绍了使用基于非病毒蛋白的纳米颗粒进行体外和体内核酸递送所取得的进展，同时详细阐述了使这些材料能够用于纳米颗粒制剂和药物递送的关键物理化学特性。最后，我们评论了与基于蛋白质的核酸递送系统用于治疗应用的转化相关的前景和未解决的挑战。