2023 World Conference on Lung Cancer (Posters)-P1.11. Application of the CRISPR/Cas9-based Gene Editing Technology for the Treatment of NUT Carcinoma

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Researchers from Sungkyunkwan University in South Korea have investigated the potential of CRISPR/Cas9-based gene editing technology for the treatment of NUT carcinoma, a rare and aggressive form of cancer with limited treatment options. NUT carcinoma is characterized by the expression of the NUTM1 fusion protein, which is responsible for driving oncogenesis. The study aimed to assess the effectiveness of CRISPR/Cas9-mediated knockout of NUTM1 in suppressing tumor growth and inducing differentiation.<br /><br />To evaluate the therapeutic potential of CRISPR/Cas9, the researchers performed spatial transcriptome analysis on cancer tissue samples with NUTM1 fusion. Single guide RNAs (sgRNAs) were designed to target NUTM1, and their efficiency was assessed using deep sequencing. The CRISPR/Cas9 system was introduced into NUTM1 fusion cells using virus-like particles (VLPs), and the inhibitory effect on NUTM1 expression was confirmed through in vitro assays.<br /><br />The results showed that the CRISPR/Cas9 system achieved nearly 90% editing efficiency in the targeted region, leading to significant reduction in cell growth rate and induction of differentiation in a subset of cells. Gene expression analysis revealed upregulation of genes involved in differentiation and regulation of cell shape, and downregulation of genes involved in transcription activation, cell cycle progression, and regulation of oncogenes.<br /><br />These findings suggest that CRISPR/Cas9-mediated suppression of NUTM1 could be a promising approach for the treatment of NUT carcinoma, especially when combined with other therapies. The use of spatial transcriptomics and RNA sequencing allowed for the identification of changes in gene expression, providing valuable insights into the potential mechanisms underlying NUT carcinoma.<br /><br />Further studies are needed to investigate the efficacy of NUTM1 suppression in preclinical and clinical settings. However, this research offers hope for the development of new treatments for NUT carcinoma, which currently has a poor prognosis. The study was supported by grants from the National Research Foundation of Korea.

Asset Subtitle

Juyoung Choi

Meta Tag

Speaker Juyoung Choi

Topic Tumor Biology: Translational Biology - Omics and New Technologies

Keywords

CRISPR/Cas9-based gene editing

NUT carcinoma

treatment options

NUTM1 fusion protein

oncogenesis

tumor growth suppression

differentiation induction

spatial transcriptome analysis

sgRNAs

editing efficiency