Departments of Biomedical Engineering, Ophthalmology, Oncology, Neurosurgery, Materials Science & Engineering, and Chemical & Biomolecular Engineering, Translational Tissue Engineering Center and Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, 400 North Broadway, Smith Building 5017, Baltimore, MD, 21231, USA.
Adv Healthc Mater. 2022 Apr;11(7):e2102145. doi: 10.1002/adhm.202102145. Epub 2022 Jan 17.
Genetic medicine has great potential to treat the underlying causes of many human diseases with exquisite precision, but the field has historically been stymied by delivery as the central challenge. Nanoparticles, engineered constructs the size of natural viruses, are being designed to more closely mimic the delivery efficiency of viruses, while enabling the advantages of increased safety, cargo-carrying flexibility, specific targeting, and ease in manufacturing. The speed in which nonviral gene transfer nanoparticles are making progress in the clinic is accelerating, with clinical validation of multiple nonviral nucleic acid delivery nanoparticle formulations recently FDA approved for both expression and for silencing of genes. While much of this progress has been with lipid nanoparticle formulations, significant development is being made with other nanomaterials for gene transfer as well, with favorable attributes such as biodegradability, scalability, and cell targeting. This review highlights the state of the field, current challenges in delivery, and opportunities for engineered nanomaterials to meet these challenges, including enabling long-term therapeutic gene editing. Delivery technology utilizing different kinds of nanomaterials and varying cargos for gene transfer (DNA, mRNA, and ribonucleoproteins) are discussed. Clinical applications are presented, including for the treatment of genetic diseases such as cystic fibrosis.
基因医学具有通过高度精确性治疗许多人类疾病根本原因的巨大潜力，但该领域在历史上一直受到传递这一核心挑战的阻碍。纳米颗粒是一种工程构建体，大小与天然病毒相当，旨在更接近地模拟病毒的传递效率，同时具有提高安全性、货物携带灵活性、靶向特异性和制造简便性的优势。非病毒基因传递纳米颗粒在临床中的进展速度正在加快，最近 FDA 批准了多种非病毒核酸递送纳米颗粒制剂用于基因表达和沉默。尽管大部分进展都是基于脂质纳米颗粒制剂，但在基因传递方面，其他纳米材料也取得了重大进展，具有生物降解性、可扩展性和细胞靶向性等有利属性。本文综述了该领域的现状、传递方面的当前挑战以及工程纳米材料应对这些挑战的机会，包括实现长期治疗性基因编辑。讨论了用于基因传递的不同种类纳米材料和不同载体的传递技术（DNA、mRNA 和核糖核蛋白）。还介绍了临床应用，包括囊性纤维化等遗传疾病的治疗。
