Haploinsufficiency in disease can be overcome by boosting gene expression with CRISPR 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.

中文翻译：

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病理基因表达的基因治疗

疾病中的单倍剂量不足可以通过使用 CRISPR 增强基因表达来克服。当一个基因的一个拷贝在功能上丢失时，就会出现单倍剂量不足，通常是通过无意义或移码突变或小的染色体缺失。由此产生的单等位基因表达没有被完整的等位基因充分补偿，最终导致基因产物的表达降低并导致病理表型 (1)。根植于基因表达不足的疾病有哪些治疗选择？一种可能的可行选择是通过以靶向方式增强基因转录来恢复正常基因表达水平。在本期第 246 页上，Matharu 等人。(2) 报告了一种基于 CRISPR 的基因激活方法，该方法可以以组织特异性方式增加正常内源基因的表达，