ACS applied materials & interfacesJun 2, 2026

Lipid Nanoparticles Designed to Deliver Gene Editing Tools to Fibroblasts for Treating Lung Fibrosis by Silencing HSP47

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 3, 2026

Abstract

Lipid nanoparticles (LNPs) effectively deliver CRISPR/Cas9 components to fibroblasts, achieving significant HSP47 knockdown.

HSP47 regulates collagen synthesis and fibrosis, making it a potential target for treating pulmonary fibrosis.
Challenges in drug delivery have hindered the verification of therapies targeting HSP47.
The developed LNPs can co-deliver Cas9 mRNA and sgHSP47 specifically to fibroblasts.
Incorporating a cationic molecule, DOTAP, enhances the uptake efficiency of LNPs in various cell lines.
Effective HSP47 knockdown in L929 cells and C57BL/6 mice results in reduced collagen deposition and fibroblast activation in a model of idiopathic pulmonary fibrosis.

Simplified

Heat shock protein 47 (HSP47) regulates collagen synthesis and fibrosis, which makes it a promising target for controlling pulmonary fibrosis. However, challenges such as cell-selective and efficient drug delivery continue to impede the verification and translation of HSP47-targeted therapies. The CRISPR/Cas9 system can effectively inhibit the overexpression of HSP47 within fibrotic lesions while significantly reducing off-target effects. This study develops a class of lipid nanoparticles (LNPs) capable of codelivering Cas9 mRNA and sgHSP47 to fibroblasts. By incorporation of an additional cationic effector molecule, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), these LNPs achieve differential delivery across various cell lines and markedly enhance uptake efficiency in fibroblasts. This system mediates effective HSP47 knockdown in L929 cells and the lungs of C57BL/6 mice, leading to reduced collagen deposition and fibroblast activation in bleomycin-induced idiopathic pulmonary fibrosis (IPF) mice. This LNP platform holds substantial potential for gene editing-based IPF therapy and provides valuable insights for the efficient and selective delivery of CRISPR/Cas9 systems.

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Lipid Nanoparticles Designed to Deliver Gene Editing Tools to Fibroblasts for Treating Lung Fibrosis by Silencing HSP47

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