Survival motor neuron 2 (SMN2) pre-mRNA (SMN2)

Survival motor neuron 2 (SMN2) pre-mRNA is a critical therapeutic target for the treatment of spinal muscular atrophy (SMA), a neurodegenerative disorder characterized by the progressive loss of motor neurons. While the SMN1 gene is the primary producer of functional SMN protein, SMN2 serves as a nearly identical paralog that typically produces only a small fraction of full-length, functional protein due to a C-to-T substitution in exon 7 that causes it to be spliced out (PubMed: 28122168). Therapeutic strategies focus on modulating the splicing of SMN2 pre-mRNA to promote the inclusion of exon 7, thereby increasing the levels of functional SMN protein (PubMed: 32763158). This is achieved through antisense oligonucleotides like nusinersen, which block intronic splicing silencers, or small molecules like risdiplam, which stabilize the interaction between the spliceosome and the SMN2 transcript (NIH: NBK1352). By compensating for the deficiency of SMN1, these interventions preserve motor neuron function and significantly improve clinical outcomes in SMA patients. This pathway represents a landmark in RNA-targeted therapeutics for genetic diseases.

Other names

SMN2 geneSurvival motor neuron 2, centromericSMNCSurvival of motor neuron 2, centromericC-SMNSMN2 transcript

Splicing modulation to promote the inclusion of exon 7 in the SMN2 mRNA transcript, thereby increasing the production of full-length, functional SMN protein (PubMed: 28122168, PubMed: 32763158).