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Updated: Jun 14, 2025
CRISPR Gene Editing Tool for MicroRNA Cluster Network Analysis
Published on: April 25, 2022
Immunoliposome-based targeted delivery of the CRISPR/Cas9gRNA-IL30 complex inhibits prostate cancer and prolongs
Cristiano Fieni1,2, Carlo Sorrentino1,2, Stefania Livia Ciummo1,2
1Department of Medicine and Sciences of Aging, "G. d'Annunzio" University of Chieti-Pescara, 66100, Chieti, Italy.
Abstract:
The development of selective and nontoxic immunotherapy targeting prostate cancer (PC) is challenging. Interleukin (IL)30 plays immunoinhibitory and oncogenic roles in PC, and its tumor-specific suppression may have significant clinical implications. CRISPR/Cas9-mediated IL30 gene deletion in PC xenografts using anti-PSCA antibody-driven lipid nanocomplexes (Cas9gRNA-hIL30-PSCA NxPs) revealed significant genome editing efficiency and circulation stability without off-target effects or organ toxicity. Biweekly intravenous administration of Cas9gRNA-hIL30-PSCA NxPs to PC-bearing mice inhibited tumor growth and metastasis and improved survival. Mechanistically, Cas9gRNA-hIL30-PSCA NxPs suppressed ANGPTL 1/2/4, IL1β, CCL2, CXCL1/6, SERPINE1-F1, EFNB2, PLG, PF4, VEGFA, VEGFD, ANG, TGFβ1, EGF and HGF expression in human PC cells while upregulated CDH1, DKK3 and PTEN expression, leading to low proliferation and extensive ischemic necrosis. In the syngeneic PC model, IL30-targeting immunoliposomes downregulated NFKB1 expression and prevented intratumoral influx of CD11b+Gr-1+MDCs, Foxp3+Tregs, and NKp46+RORγt+ILC3, and prolonged host survival by inhibiting tumor progression. This study serves as a proof of principle that immunoliposome-based targeted delivery of Cas9gRNA-IL30 represent a potentially safe and effective strategy for PC treatment.
Insights
Targeting Interleukin 30 (IL30) with CRISPR/Cas9 gene editing via antibody-targeted nanoparticles effectively inhibited prostate cancer growth and metastasis in mice, offering a promising new immunotherapy.
Area of Science:
- Immunotherapy
- Gene Editing
- Prostate Cancer Research
Background:
- Developing selective and non-toxic immunotherapies for prostate cancer (PC) remains a significant challenge.
- Interleukin 30 (IL30) exhibits immunoinhibitory and oncogenic functions in PC, making its tumor-specific suppression a potential therapeutic strategy.
Purpose of the Study:
- To investigate the efficacy and safety of CRISPR/Cas9-mediated IL30 gene deletion for prostate cancer treatment.
- To evaluate the potential of anti-PSCA antibody-driven lipid nanocomplexes for targeted delivery of gene-editing components.
Main Methods:
- CRISPR/Cas9-mediated IL30 gene deletion was performed using anti-PSCA antibody-driven lipid nanocomplexes (Cas9gRNA-hIL30-PSCA NxPs) in PC xenografts.
- The therapeutic effect was assessed in mouse models, including evaluation of tumor growth, metastasis, survival, and immune cell infiltration.
- Gene expression analysis was conducted to understand the underlying molecular mechanisms.
Main Results:
- Cas9gRNA-hIL30-PSCA NxPs demonstrated high genome editing efficiency, circulation stability, and no observed off-target effects or organ toxicity.
- Intravenous administration of the therapy significantly inhibited tumor growth and metastasis while improving survival in PC-bearing mice.
- The treatment modulated the expression of multiple genes involved in cell proliferation, angiogenesis, and immune response, and altered the tumor microenvironment by reducing specific immune cell populations.
Conclusions:
- Targeted delivery of CRISPR/Cas9-mediated IL30 gene deletion using immunoliposomes represents a potentially safe and effective strategy for prostate cancer treatment.
- This approach offers a proof-of-principle for utilizing advanced gene-editing technology in cancer immunotherapy.
