2. Academic Validation
  3. Species-dependent in vivo mRNA delivery and cellular responses to nanoparticles

Species-dependent in vivo mRNA delivery and cellular responses to nanoparticles

  • Nat Nanotechnol. 2022 Mar;17(3):310-318. doi: 10.1038/s41565-021-01030-y.
Marine Z C Hatit # 1,  Melissa P Lokugamage # 1,  Curtis N Dobrowolski # 1,  Kalina Paunovska 1,  Huanzhen Ni 1,  Kun Zhao 1,  Daryll Vanover 2,  Jared Beyersdorf 2,  Hannah E Peck 2,  David Loughrey 1,  Manaka Sato 1,  Ana Cristian 1,  Philip J Santangelo 1 2,  James E Dahlman 3
Affiliations

Affiliations

  • 1 Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
  • 2 Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
  • 3 Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA. [email protected].
  • # Contributed equally.
PMID: 35132167 DOI: 10.1038/s41565-021-01030-y
Abstract

Nanoparticles are tested in mice and non-human primates before being selected for clinical trials. Yet the extent to which mRNA delivery, as well as the cellular response to mRNA drug delivery vehicles, is conserved across species in vivo is unknown. Using a species-independent DNA barcoding system, we have compared how 89 lipid nanoparticles deliver mRNA in mice with humanized livers, primatized livers and four controls: mice with 'murinized' livers as well as wild-type BL/6, Balb/C and NZB/BlNJ mice. We assessed whether functional delivery results in murine, non-human primate and human hepatocytes can be used to predict delivery in the other species in vivo. By analysing in vivo hepatocytes by RNA sequencing, we identified species-dependent responses to lipid nanoparticles, including mRNA translation and endocytosis. These data support an evidence-based approach to making small-animal preclinical nanoparticle studies more predictive, thereby accelerating the development of RNA therapies.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-134781
    ≥98.0%, Ionizable Lipid