2. Academic Validation
  3. Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing

Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing

  • Nat Biotechnol. 2023 Oct;41(10):1410-1415. doi: 10.1038/s41587-023-01679-x.
Bowen Li # 1 2 3 4,  Rajith Singh Manan # 1 2,  Shun-Qing Liang # 5,  Akiva Gordon 1 2,  Allen Jiang 1 2,  Andrew Varley 3,  Guangping Gao 5 6,  Robert Langer 1 2 7 8 9,  Wen Xue 10 11,  Daniel Anderson 12 13 14 15 16
Affiliations

Affiliations

  • 1 David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 2 Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 3 Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
  • 4 Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
  • 5 RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
  • 6 Horae Gene Therapy Center and Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.
  • 7 Department of Anesthesiology, Boston Children's Hospital, Boston, MA, USA.
  • 8 Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 9 Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 10 RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA. [email protected].
  • 11 Li Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, MA, USA. [email protected].
  • 12 David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. [email protected].
  • 13 Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. [email protected].
  • 14 Department of Anesthesiology, Boston Children's Hospital, Boston, MA, USA. [email protected].
  • 15 Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA. [email protected].
  • 16 Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA. [email protected].
  • # Contributed equally.
PMID: 36997680 DOI: 10.1038/s41587-023-01679-x
Abstract

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.

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