CRISPR/Cas13a is a powerful RNA editing system with enormous clinical potential for screening drug targets and targeting oncogenes or immune checkpoints that are currently untreatable or unavailable for drug use. The immunosuppressive tumor microenvironment and acquired drug resistance in colorectal cancer (CRC) are important reasons for the low clinical response to PD-1/PD-L1 immunotherapy. T cell immunoglobulin mucin-3 (TIM3), as a novel immune checkpoint molecule, can significantly inhibit T cell activity, leading to a "depletion phenomenon" of T cells and specifically disrupting the ability of HMGB1 to induce immunogenic tumor cell death (ICD). In view of this, the team led by Professor Zhang Bingchen from Southern Medical University has designed a self-assembled nano prodrug drug delivery system based on SN38 and CRISPR/Cas13a with spatial level unsealing properties. The external coating is constructed using an amphiphilic NIR-II probe, and the nano prodrug can achieve tumor imaging and intracellular drug cascade release in the tumor microenvironment. The study found that the drug system exhibits efficient RNA editing ability, induces ICD effect while synergistically activating the cGAS STING natural immune pathway, significantly promotes DC cell maturation and NK cell proliferation, and induces cytotoxic T cell-mediated tumor immune infiltration. It demonstrates significant therapeutic properties in PD-L1 resistant CRC subcutaneous and in situ models.
The study was published on September 3, 2023 in the international journal Advanced Functional Materials, titled Precise RNA Editing: Cascade Self Encooking Dual Prodrug Nanoassemblies Based on CRISPR/Cas13a for Pleotrophic Immunotherapy of PD-L1-Resistant Colored Cancer.
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Figure 1. The study was published in the international journal Advanced Functional Materials
Figure 2. Images in the article
Figure 3. Cell culture in this study was conducted using Opsey fetal bovine serum
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