清脆的
聚乙烯亚胺
化学
表面改性
内体
苯硼酸
纳米技术
组合化学
生物物理学
生物化学
材料科学
转染
生物
基因
物理化学
催化作用
细胞内
作者
Naoto Yoshinaga,Joyce K. Zhou,Cong Xu,Chai Hoon Quek,Yuefei Zhu,Ding Tang,Lin W. Hung,Sarah A. Najjar,Chin Ying Angela Shiu,Kara Gross Margolis,Yeh‐Hsing Lao,Kam W. Leong
出处
期刊:Nano Letters
[American Chemical Society]
日期:2023-01-17
卷期号:23 (3): 757-764
被引量:9
标识
DOI:10.1021/acs.nanolett.2c02306
摘要
Effective delivery of the CRISPR-Cas9 components is crucial to realizing the therapeutic potential. Although many delivery approaches have been developed for this application, oral delivery has not been explored due to the degradative nature of the gastrointestinal tract. For this issue, we developed a series of novel phenylboronic acid (PBA)-functionalized chitosan-polyethylenimine (CS-PEI) polymers for oral CRISPR delivery. PBA functionalization equipped the polyplex with higher stability, smooth transport across the mucus, and efficient endosomal escape and cytosolic unpackaging in the cells. From a library of 12 PBA-functionalized CS-PEI polyplexes, we identified a formulation that showed the most effective penetration in the intestinal mucosa after oral gavage to mice. The optimized formulation performed feasible CRISPR-mediated downregulation of the target protein and reduction in the downstream cholesterol. As the first oral CRISPR carrier, this study suggests the potential of addressing the needs of both local and systemic editing in a patient-compliant manner.
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