Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing

被引：125
|
作者：
Li, Bowen [1 ,2 ,3 ,4 ]
Manan, Rajith Singh [1 ,2 ]
Liang, Shun-Qing [5 ]
Gordon, Akiva [1 ,2 ]
Jiang, Allen [1 ,2 ]
Varley, Andrew [3 ]
Gao, Guangping [5 ,6 ]
Langer, Robert [1 ,2 ,7 ,8 ,9 ]
Xue, Wen [5 ,10 ]
Anderson, Daniel [1 ,2 ,7 ,8 ,9 ]
机构：
[1] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA
[2] MIT, Dept Chem Engn, Cambridge, MA 02139 USA
[3] Univ Toronto, Leslie Dan Fac Pharm, Dept Pharmaceut Sci, Toronto, ON, Canada
[4] Univ Toronto, Inst Biomed Engn, Toronto, ON, Canada
[5] Univ Massachusetts, RNA Therapeut Inst, Med Sch, Worcester, MA 01655 USA
[6] Univ Massachusetts, Horae Gene Therapy Ctr, Dept Microbiol & Physiol Syst, Med Sch, Worcester, MA USA
[7] Boston Childrens Hosp, Dept Anesthesiol, Boston, MA 02115 USA
[8] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA
[9] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA
[10] Univ Massachusetts, Li Weibo Inst Rare Dis Res, Med Sch, Worcester, MA 01655 USA
来源：
NATURE BIOTECHNOLOGY | 2023年 / 41卷 / 10期
基金：
美国国家卫生研究院; 加拿大健康研究院; 加拿大创新基金会;
关键词：
IN-VIVO; LIPID NANOPARTICLES; LUNG DEVELOPMENT; GENE; REGENERATION; OPTIMIZATION; MECHANISMS; VECTORS; DISEASE; REPAIR;
D O I：
10.1038/s41587-023-01679-x
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
The expanding applications of nonviral genomic medicines in the lung remain restricted by delivery challenges. Here, leveraging a high-throughput platform, we synthesize and screen a combinatorial library of biodegradable ionizable lipids to build inhalable delivery vehicles for messenger RNA and CRISPR-Cas9 gene editors. Lead lipid nanoparticles are amenable for repeated intratracheal dosing and could achieve efficient gene editing in lung epithelium, providing avenues for gene therapy of congenital lung diseases. A high-throughput screen improves lipid nanoparticle delivery of gene editors in the lung.
引用
收藏
页码：1410 / +
页数：12
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