Cystathionine beta-synthase mRNA (CBS mRNA)

Cystathionine beta-synthase (CBS) mRNA is the transcript encoding the CBS enzyme, which is the rate-limiting catalyst in the transsulfuration pathway (UniProt P35520). This enzyme converts homocysteine to cystathionine, a process vital for maintaining low systemic homocysteine levels and producing downstream metabolites like cysteine and hydrogen sulfide (PubMed: 28236033). Mutations in the CBS gene lead to classical homocystinuria, characterized by toxic accumulation of homocysteine, leading to multi-systemic issues including thromboembolism and intellectual disability (NIH GARD). CBS mRNA is a primary target for mRNA replacement therapy, where exogenous, synthetic mRNA (e.g., mRNA-3924) is delivered to the liver to restore functional enzyme production (Moderna Pipeline). This therapeutic strategy aims to correct the metabolic imbalance without altering the patient's genome. Efficacy is primarily monitored through the reduction of total plasma homocysteine levels (PubMed: 30635457). Additionally, the regulation of CBS mRNA levels is relevant in Down syndrome, where its overexpression contributes to metabolic disturbances (PubMed: 21684334). Safety considerations for targeting CBS mRNA via replacement include potential immune reactions to the lipid nanoparticle delivery vehicle and the need for precise dosing to avoid excessive hydrogen sulfide production.

Other names

CBS transcriptCystathionine beta-synthase messenger RNA

mRNA replacement therapy designed to encode the functional cystathionine beta-synthase enzyme, thereby restoring the transsulfuration pathway and reducing toxic homocysteine levels (Moderna Pipeline).