PerspectiveTHERAPEUTICS

Gene therapy for pathologic gene expression

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Science  18 Jan 2019:
Vol. 363, Issue 6424, pp. 231-232
DOI: 10.1126/science.aaw0635

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Summary

Haploinsufficiency arises when one copy of a gene is functionally lost, often through nonsense or frameshift mutations or small chromosomal deletions. The resulting monoallelic expression is not sufficiently compensated for by the intact allele, ultimately leading to decreased expression of the gene product and resulting in pathologic phenotypes (1). What are the therapeutic options for diseases rooted in insufficient gene expression? One possible viable option is to restore normal gene expression levels by enhancing their transcription in a targeted fashion. On page 246 in this issue, Matharu et al. (2) report a CRISPR-based gene-activation approach that can increase the expression of normal endogenous genes in a tissue-specific manner, setting the stage for the development of new gene-regulating therapies for gene dosage–associated diseases.