Combinatorial library of chalcogen-containing lipidoids for intracellular delivery of genome-editing proteins

  • Biomaterials. 2018 Sep:178:652-662. doi: 10.1016/j.biomaterials.2018.03.011.
Yamin Li  1 ,  Tao Yang  2 ,  Yingjie Yu  1 ,  Nicola Shi  1 ,  Liu Yang  1 ,  Zachary Glass  1 ,  Justin Bolinger  1 ,  Isaac James Finkel  1 ,  Wenhan Li  1 ,  Qiaobing Xu  3
Affiliations
  • 1. Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
  • 2. Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610065, PR China.
  • 3. Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA. Electronic address: [email protected].
PMID: 29549971 DOI: 10.1016/j.biomaterials.2018.03.011
Abstract

Protein based therapeutics with high specificities and low off-target effects are used for transient and accurate manipulation of cell functions. However, developing safe and efficient carriers for intracellular delivery of active therapeutic proteins is a long-standing challenge. Here we report a combinatorial library of chalcogen (O, S, Se) containing lipidoid nanoparticles (LNPs) as efficient nanocarriers for intracellular delivery of negatively supercharged Cre recombinase ((-30)GFP-Cre) and anionic Cas9:single-guide RNA (Cas9:sgRNA) ribonucleoprotein (RNP) for genome editing. The structure-activity relationship between the lipidoids and intracellular protein delivery efficiencies was explored and it was demonstrated that the newly developed LNPs are effective for gene recombination in vivo.

Keywords
CRISPR/Cas9; Genome editing; Lipidoids; Protein delivery.
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