The modified cells exhibit distinct growth patterns, apoptotic activity, and cytokine expression, as well as increased CD8+ T cell infiltration, providing a comprehensive platform to study how DNArepairdefects can influence tumor dynamics and immune interactions. This technology employs CRISPR-mediated inactivation of the MLH1 gene within CT26 and MC-38 murine colorectal tumor cell lines to simulate DNA mismatch repair deficiency, resulting in microsatellite instability. - Provides mechanistic insights into how DNA mismatch repair deficiency leads to microsatellite instability and influences tumor growth.
These engineered cell lines allow researchers to compare tumors with intact and defectiveDNArepair mechanisms under identical conditions. A CRISPR-based technology was developed to inactivate the MLH1 gene in four distinct murine cancer cell lines—CT26, MC-38, Panc02, and 4T1—yielding isogenic models that accurately mirror the microsatellite instability associated with DNA mismatch repair deficiencies. This technology stands out due to its precise replication of microsatellite instability effects, enabling direct investigations into the role of DNArepair deficiency in tumor immunogenicity.
Scientists from University of Pittsburgh have developed a novel approach to target cancer cells through the insertion of a “suicide gene” (HSV1-tk) into key gene fusion areas of the cancer genome. • Creation of this unique breakpoint, present only in cancer tissue provides a target for therapeutic intervention which is less likely to result in drug resistance through gene mutation. Scientists from University of Pittsburgh have developed a novel approach to target cancer cells through the insertion of a “suicide gene” (HSV1-tk) into key gene fusion areas of the cancer genome.