Screening methods for spinal muscular atrophy
Disclosed herein are compositions and methods for treatment of spinal muscular atrophy (SMA). In certain embodiments, compounds are provided that increase full-length survival of motor neuron (SMN) protein production by an SMN2 gene.
1. A vector comprising: a survival motor neuron (SMN) promoter selected from the group consisting of a survival motor neuron 1 (SMN1) promoter and a survival motor neuron 2 (SMN2) promoter; a transcription start site; exons 1-8 of the SMN gene; a truncated intron 6 of the SMN gene; and a reporter gene.
2. The vector of claim 1 , wherein the reporter gene encodes a reporter protein selected from the group consisting of luciferase, green fluorescent protein, and red fluorescent protein.
3. The vector of claim 1 , wherein the truncated intron 6 comprises a 2 kilobase deletion.
4. A host cell comprising the vector of claim 1 .
5. The host cell of claim 4 selected from the group consisting of a C33 cell; a HEK-293 cell; a spinal muscular atrophy type 1 (GM3813) fibroblast; and a 3814 (GM3814) fibroblast.
6. A vector comprising: a survival motor neuron 1 (SMN1) promoter; a transcription start site; exons 1-8 of the SMN1 gene; a truncated intron 6 of the SMN1 gene; and a reporter gene.
7. The vector of claim 6 , wherein the reporter gene encodes a reporter protein selected from the group consisting of luciferase, green fluorescent protein, and red fluorescent protein.
8. The vector of claim 6 , wherein the truncated intron 6 comprises a 2 kilobase deletion.
9. A host cell comprising the vector of claim 6 .
10. The host cell of claim 9 selected from the group consisting of a C33 cell; a HEK-293 cell; a spinal muscular atrophy type 1 (GM3813) fibroblast; and a 3814 (GM3814) fibroblast.
11. A vector comprising: a survival motor neuron 2 (SMN2) promoter; a transcription start site; exons 1-8 of the SMN2 gene; a truncated intron 6 of the SMN2 gene; and a reporter gene.
12. The vector of claim 11 , wherein the reporter gene encodes a reporter protein selected from the group consisting of luciferase, green fluorescent protein, and red fluorescent protein.
13. The vector of claim 11 , wherein the truncated intron 6 comprises a 2 kilobase deletion.
14. A host cell comprising the vector of claim 11 .
15. The host cell of claim 14 selected from the group consisting of a C33 cell; a HEK-293 cell; a spinal muscular atrophy type 1 (GM3813) fibroblast; and a 3814 (GM3814) fibroblast.