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. 2023 Aug 25;28(8):3182–3193. doi: 10.1038/s41380-023-02208-7

Fig. 2. Therapeutic strategies for AS and PWS.

Fig. 2

Schematic shows the imprinting domain in human chromosome 15q11-q13 with potential epigenetic therapeutic candidates for (a) AS and (b) PWS. Genes in dark blue are exclusively expressed from the paternal chromosome while genes in purple are expressed from the maternal chromosome in neuronal cell type specific manner (gray bar, imprinted gene; biallelic expressed gene, black bar). In the case of AS, the loss of UBE3A expression in the maternal allele by different mechanisms is the cause. The principle of epigenetics-based therapy is to reactivate the paternal allele’s expression of UBE3A in neurons. The current approach is to inhibit the expression of antisense of UBE3A via small molecule, ASO, CRISPR/Cas9, or Cas13. In the case of PWS, where more than one paternally expressed gene is in the candidate region, the optimal approach is to manipulate the imprinting center region to reactivate the expression of silenced genes from the maternal chromosome. Current approaches include DNA methylation inhibitor, small molecule for histone modifications and others, CRISPR/dCas9 gene editing. Created with BioRender.com.