Serpin family B member 9 mRNA (SERPINB9 mRNA)

Serpin family B member 9 (SERPINB9) mRNA encodes a nucleocytoplasmic protein that serves as the primary endogenous inhibitor of Granzyme B, a potent pro-apoptotic protease released by cytotoxic T lymphocytes and natural killer cells. By neutralizing Granzyme B, the SERPINB9 protein protects cells from misdirected or premature apoptosis, a function essential for the survival of the immune cells themselves. However, many tumors and virally infected cells overexpress SERPINB9 to evade immune-mediated destruction, leading to resistance against immunotherapies such as immune checkpoint inhibitors and CAR T-cell therapy. Targeting SERPINB9 mRNA using RNA interference (RNAi) or antisense oligonucleotides (ASOs) is a therapeutic strategy aimed at reducing protein levels to restore the susceptibility of resistant cancer cells to Granzyme B-induced death. Beyond oncology, SERPINB9 is involved in regulating inflammatory responses through the inhibition of Caspase-1 and plays roles in autoinflammatory diseases and transplant rejection. Current research focuses on utilizing nanoparticle-delivered RNA therapeutics to selectively knockdown SERPINB9 in the tumor microenvironment to enhance the efficacy of existing immunotherapies.

Other names

PI-9 mRNAProtease inhibitor 9 mRNACytoplasmic antiproteinase 3 mRNACAP-3 mRNASerine protease inhibitor 6 mRNA

RNA interference (RNAi) or antisense inhibition to reduce protein expression, thereby sensitizing cells to Granzyme B-mediated apoptosis.