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Gene-editing technology shows great potential in glioblastoma (GBM) therapy. Due to the complexity of GBM pathogenesis, a single gene-editing-based therapy is unlikely to be successful; therefore, a multi-gene knockout strategy is preferred for effective GBM inhibition. Here, a non-invasive, biodegradable brain-targeted CRISPR/Cas12a nanocapsule is used that simultaneously targeted dual oncogenes, EGFR and PLK1, for effective GBM therapy. This cargo nanoencapsulation technology enables the CRISPR/Cas12a system to achieve extended blood half-life, efficient blood-brain barrier (BBB) penetration, active tumor targeting, and selective release. In U87MG cells, the combinatorial gene editing system resulted in 61% and 33% knockout of EGFR and PLK1, respectively. Following systemic administration, the CRISPR/Cas12a system demonstrated promising brain tumor accumulation that led to extensive EGFR and PLK1 gene editing in both U87MG and patient-derived GSC xenograft mouse models with negligible off-target gene editing detected through NGS. Additionally, CRISPR/Cas12a nanocapsules that concurrently targeted the EGFR and PLK1 oncogenes showed superior tumor growth suppression and significantly improved the median survival time relative to nanocapsules containing single oncogene knockouts, signifying the potency of the multi-oncogene targeting strategy. The findings indicate that utilization of the CRISPR/Cas12a combinatorial gene editing technique presents a practical option for gene therapy in GBM.
Pubmed ID: 38943253
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Privately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsWeb application that helps design, evaluate and clone guide sequences for the CRISPR/Cas9 system. This sgRNA design tool assists with guide selection in a variety of genomes and pre-calculated results for all human coding exons as a UCSC Genome Browser track.
View all literature mentionsWeb application that searches for potential off-target sites of Cas9 RNA-guided endonucleases. Enables searching for potential off-target sites in any sequenced genome rapidly without limiting PAM sequence or number of mismatched bases.
View all literature mentionsMus musculus with name BALB/cAnN-Foxn1nu/nu/Rj from IMSR.
View all literature mentionslaboratory mouse with name BALB/cAnNCrl from MGI.
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