DataVXACS NanoPaper
journal article·2025-04-15

Lipid Nanoparticles for In Vivo Lung Delivery of CRISPR-Cas9 Ribonucleoproteins Allow Gene Editing of Clinical Targets

Rebecca M. Haley, Marshall S. Padilla, Rakan D. El-Mayta, Ryann A. Joseph, Jesse A. Weber, Christian G. Figueroa-Espada, Alvin J. Mukalel, Adele S. Ricciardi, Rohan Palanki, Hannah C. Geisler, Matthew T. Jester, Beverly L. Davidson, Michael J. Mitchell

ACS Nano· Volume 19· Issue 14
Publisher page
Source abstract

Abstract

In the past 10 years, CRISPR-Cas9 has revolutionized the gene-editing field due to its modularity, simplicity, and efficacy. It has been applied for the creation of in vivo models, to further understand human biology, and toward the curing of genetic diseases. However, there remain significant delivery barriers for CRISPR-Cas9 application in the clinic, especially for in vivo and extrahepatic applications. In this work, high-throughput molecular barcoding techniques were used alongside traditional screening methodologies to simultaneously evaluate LNP formulations encapsulating ribonucleoproteins (RNPs) for in vitro gene-editing efficiency and in vivo biodistribution. This resulted in the identification of a lung-tropic LNP formulation, which shows efficient gene editing in endothelial and epithelial cells within the lung, targeting both model reporter and clinically relevant genomic targets. Further, this LNP shows no off-target indel formation in the liver, making it a highly specific extrahepatic delivery system for lung-editing applications.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: CRISPR and Genetic Engineering · RNA Interference and Gene Delivery · Viral Infections and Immunology Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Bioengineering

University of Pennsylvania

Raymond G. Perelman Center for Cellular and Molecular Therapeutics

The Children’s Hospital of Philadelphia

Cell and Molecular Biology Graduate Group, Perelman School of Medicine

Department of Pathology and Laboratory Medicine

Penn Institute for RNA Innovation, Perelman School of Medicine

Funding

National Center for Advancing Translational Sciences · National Science Foundation Graduate Research Fellowship Program · National Cancer Institute · University of Pennsylvania · National Heart, Lung, and Blood Institute · National Institute of Dental and Craniofacial Research · Center for Undergraduate Research and Fellowships, University of Pennsylvania · Cystic Fibrosis Foundation · American Cancer Society · Division of Chemical, Bioengineering, Environmental, and Transport Systems · Burroughs Wellcome Fund · Foundation for the National Institutes of Health · Hispanic Scholarship Fund · Abramson Cancer Center · Advancing Women in Engineering · Center for Innovation & Precision Dentistry, University of Pennsylvania

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