Optimized LNP enables CRISPR in hard-to-transfect cells

Xinpu Yang and co-authors reported an optimized lipid nanoparticle, or LNP, platform that improved CRISPR/Cas9 delivery in cell types that are typically difficult to transfect, according to a paper published on May 28 in Acta Biomaterialia. The study said the formulation was designed as a non-viral delivery system for genome editing, an area where researchers have long faced tradeoffs between delivery efficiency, toxicity and cell-type specificity. (sciencedirect.com) The authors said their engineered particles had a size below 100 nanometers, low polydispersity and high encapsulation efficiency. (booksci.cn) The paper was highlighted again on June 3 in a ScienceCrisp social-media post. (sciencedirect.com) ### Which cells did the researchers say were hardest to edit? The Acta Biomaterialia paper said the platform was tested across multiple cell types, including mesenchymal stem cells and DC2.4 cells, which the authors described as harder to modify with commercial lipid-based reagents. The paper framed that problem as a central bottleneck for CRISPR work in both functional genomics and therapeutic development. The authors wrote that conventional lipid delivery performance can vary widely across cell lines because cell membranes differ in ways that affect uptake and intracellular release. That variability, they said, has limited broader use of LNPs in hard-to-transfect cells. (sciencedirect.com) ### What did the optimized LNP actually achieve? The study reported 78.7% GFP knockout in HEK-293 cells using the optimized LNP formulation. The authors also said the particles retained that knockout efficiency after lyophilization and reconstitution, a detail that could matter for storage and handling. (sciencedirect.com) In MDA-MB-231 cells, the paper said knockout of the LCN2 gene reduced messenger RNA expression by 90.8%. The same comparison said CRISPRMAX Lipofectamine produced a 51.1% reduction in that setting. Functional assays in the paper linked LCN2 disruption to reduced cell proliferation and migration. (booksci.cn) ### Did the paper report only knockout results? The paper also reported homology-directed repair, or HDR, knock-in results. Co-delivery of CRISPR/Cas9 with a GFP HDR template produced more than 20% knock-in efficiency in HEK-293 cells and more than 8% in mesenchymal stem cells and DC2.4 cells, according to the abstract and article summaries. (ebiotrade.com) The authors said those results outperformed Lipofectamine 3000 in the same experiments. Those knock-in data matter because HDR-based editing is generally harder to achieve than simple gene disruption. The paper presented the platform as capable of supporting both knockout and precise insertion workflows in the same broader delivery framework. (ebiotrade.com) ### Who wrote the study and where was it published? The paper listed Xinpu Yang, Rui Sang, Gyorgy Hutvagner, Alex W. Hewitt, Diangeng Li, Yi Li and Wei Deng as authors. ScienceDirect and Crossref-linked records show the article under the title “An optimised lipid nanoparticle platform enables efficient CRISPR/Cas9 genome editing in hard-to-transfect cells,” with DOI 10.1016/j.actbio.2026.05.044. (sciencedirect.com) Rui Sang’s ORCID profile identifies her as a research associate at the University of New South Wales working on nanoparticle-based technology for cancer treatment and CRISPR-based gene therapy and diagnostic applications. (booksci.cn) ### Where can readers find the next step? ScienceCrisp pointed readers on June 3 to the paper and related materials in a social-media post. The full article is available through Acta Biomaterialia on ScienceDirect, where the journal lists it among recent articles in press. (sciencedirect.com) (orcid.org) (sciencedirect.com)