The correction of SMN2 gene splicing using antisense oligonucleotides delivered with peptide carriers into SMA fibroblast cultures

Background. Spinal muscular atrophy is a severe neurodegenerative disease for which the development of therapeutic approaches and optimization of the delivery of therapeutic molecules into cells remains relevant.

Aim: to investigate the effectiveness of correcting the splicing of the SMN2 gene with antisense oligonucleotides delivered in combination with a peptide carrier into fibroblast cultures of SMA patients.

Methods. Fibroblast culture of SMA patient, antisense RNA oligonucleotides, peptide carrier. Methods of cell culture cultivation, RNA isolation and analysis, immunocytochemistry.

Results. We have shown the effectiveness of antisense oligonucleotides (ASO) for correcting the splicing of the SMN2 gene delivered by a peptide carrier containing a ligand to receptors on the surface of target cells. A significant increase in the proportion of full-length SMN transcripts and gems containing the SMN protein was found as a result of the delivery of ASO:carrier complexes to SMA fibroblast cultures.

Conclusion. These results are promising for the development of methods for the non-viral delivery of therapeutic molecules into the cells of SMA patients.

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