BCL2 mRNA

Class

Liposomal antisense oligodeoxynucleotide

Pathway

Hybridizes with and inhibits translation of BCL-2 mRNA, restoring apoptosis

BCL-2 is a protein that normally protects cells from a controlled self-destruction process called apoptosis. It does this by binding and neutralizing other proteins that would otherwise trigger the mitochondrial pathway of cell death. Many cancers, particularly lymphomas and leukemias, produce excess BCL-2, which allows malignant cells to survive despite the DNA damage and abnormal signaling that would normally mark them for elimination. This mechanism uses an antisense oligodeoxynucleotide, a short synthetic strand of nucleic acid designed to bind specifically to the messenger RNA (mRNA) that carries the genetic instructions for making BCL-2 protein. By hybridizing to this mRNA, the oligonucleotide prevents the cell's machinery from translating it into protein, reducing the supply of BCL-2 rather than blocking an already-made protein. With less BCL-2 available, the cell's apoptotic machinery is no longer restrained, and cancer cells with a survival dependence on this protein become more susceptible to programmed death. The oligonucleotide is packaged in a liposome, a fat-based particle, to protect it from degradation in the bloodstream and improve its delivery into cells. This approach broadly matters in hematologic and other cancers where BCL-2 overexpression sustains tumor cell survival.