Access to essential medicines in low and middle income countries

Spinal muscular atrophy (SMA) is a severe hereditary neuromuscular disorder that is the leading genetic cause of infant death. SMA patients become paralyzed and often die of their symptoms in a matter of months. In this work, we have identified a previously unknown gene that is affected in SMA patients, and appears to be the underlying cause of this disorder. Overexpression of this new gene in SMA mice rescues their paralysis and fatality that results from motor neuron degeneration.

Furthermore, we present an innovative new approach to CRISPR/Cas9 gene editing that eliminates the need to generate site-specific targeting plasmids for every genomic locus. Using this Self-Cloning CRISPR (scCRISPR) system, we screened a variety of gene-editing approaches and developed a CRISPR/Cas9 targeting strategy that can correct the genetic mutation that causes SMA.

In this manner we were able to restore the SMA mutation in patient cells. By combining this gene-editing approach with existing methods of in vivo gene therapy, we are working to develop a new treatment that may cure SMA mice of their neuromuscular symptoms.