Targeted CRISPR delivery inhibits prostate cancer

Italian scientists have demonstrated the potential of a targeted CRISPR-Cas9 delivery system to suppress tumour growth and metastasis in prostate cancer (PC). By employing lipid nanocomplexes conjugated with anti-prostate stem cell antigen (PSCA) antibodies, the researchers delivered the CRISPR-Cas9 system targeting the immunosuppressive interleukin-30 (IL30) gene specifically to PC cells.

By: Gorm Palmgren - Sep. 5, 2024

The study showed that biweekly intravenous administration of these Cas9gRNA-hIL30-PSCA nanocomplexes (NxPs) in PC-bearing mice significantly inhibited tumour progression and extended survival without off-target effects or organ toxicity.

This gene-editing approach suppressed a host of tumour-promoting genes, such as VEGFA, TGFβ1, and CXCL6, while upregulating tumour-suppressor genes like PTEN and CDH1, leading to reduced proliferation and extensive tumour necrosis. In an immunocompetent PC model, the IL30-targeting NxPs further reduced immune cell infiltration associated with tumour growth, including Foxp3+ regulatory T cells, prolonging host survival.

This proof-of-principle study indicates that immunoliposome-based CRISPR delivery could offer a precise, non-toxic method for treating prostate cancer.

The research was conducted by Cristiano Fieni and Emma Di Carlo at the University of Chieti-Pescara, Italy, and published in Experimental & Molecular Medicine on 4 September 2024.

To get more CRISPR Medicine News delivered to your inbox, sign up to the free weekly CMN Newsletter here.

ArticleCMN BriefsNewsLipid-based nanoparticleProstate Cancer