Biodegradable Amino-Ester Nanomaterials for Cas9 mRNA Delivery in Vitro and in Vivo.
Efficient and safe delivery of the CRISPR/Cas system is one of the key challenges for genome-editing applications in humans. Herein, we designed and synthesized a series of biodegradable lipidlike compounds containing ester groups for the delivery of mRNA-encoding Cas9. Two lead materials, termed N-methyl-1,3-propanediamine (MPA)-A and MPA-Ab, showed a tunable rate of biodegradation. MPA-A with linear ester chains was degraded dramatically faster than MPA-Ab with branched ester chains in the presence of esterase or in wild-type mice. Most importantly, MPA-A and MPA-Ab demonstrated efficient delivery of Cas9 mRNA both in vitro and in vivo. Consequently, these biodegradable lipidlike nanomaterials merit further development as genome-editing delivery tools for biological and therapeutic applications.
['Zhang|Xinfu|X|', 'Li|Bin|B|', 'Luo|Xiao|X|', 'Zhao|Weiyu|W|', 'Jiang|Justin|J|', 'Zhang|Chengxiang|C|', 'Gao|Min|M|', 'Chen|Xiaofang|X|', 'Dong|Yizhou|Y|http://orcid.org/0000-0001-5786-0659']
D000818:Animals D064113:CRISPR-Cas Systems D004952:Esters D000072669:Gene Editing D051379:Mice D049329:Nanostructures D012333:RNA, Messenger
mRNA CRISPR/Cas9 biodegradable nanomaterials genome editing lipidlike nanoparticles