Spinal muscular atrophy (SMA), a neurodegenerative disorder caused by mutations in survival motor neuron 1 (SMN1) resulting in reduced expression of the survival motor neuron (SMN) protein, is inherited in an autosomal recessive manner.SMA type 1 is the most frequent subtype of SMA characterized by onset before 6 mo of life, inability to achieve independent sitting, and rapidly progressive respiratory and bulbar deterioration, causing a mortality of >90% before 2 years of age.Currently, there have been two lifelong splice-modifying therapies (nusinersen and risdiplam), and a single-dose gene replacement therapy via i.v. onasemnogene abeparvovec for SMA type 1 patients, approved by the US Food and Drug Administration.Here, we developed recombinant adeno-associated virus serotype 9 (AAV9) containing codon-optimized human SMN1 (co-SMN1) complementary DNA (GC101) driven by cytomegalovirus (CMV) enhancer and chicken β-actin promoter with the attributes of high titer, low endotoxin, low aggregation, and a low empty capsid rate.Knowing that the degeneration and death of α-motor neurons in the spinal cord and brainstem are major manifestations of the disease, and that the AAV9 vector would not only reach the motor neurons directly but could also pass the blood-brain barrier before reaching the peripheral tissues, it seems possible that intrathecal injection of GC101 could have a favorable benefit-risk profile.The aim of this trial was to investigate the safety and efficacy of GC101 via intrathecal injection in SMA type 1 patients.