ACS Applied Materials & Interfaces
ACS Applied Materials & Interfaces
5 years ago

Biodegradable Amino-Ester Nanomaterials for Cas9 mRNA Delivery in Vitro and in Vivo

Biodegradable Amino-Ester Nanomaterials for Cas9 mRNA Delivery in Vitro and in Vivo
Xiaofang Chen, Yizhou Dong, Bin Li, Weiyu Zhao, Chengxiang Zhang, Xiao Luo, Xinfu Zhang, Min Gao, Justin Jiang
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.

Publisher URL: http://dx.doi.org/10.1021/acsami.7b08163

DOI: 10.1021/acsami.7b08163

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