使用腺相关病毒载体进行心脏基因转移的转录靶向方法。

Transcriptional Targeting Approaches in Cardiac Gene Transfer Using AAV Vectors.

作者信息

Schröder Lena C, Frank Derk, Müller Oliver J

机构信息

Department of Internal Medicine III, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.

DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, 24105 Kiel, Germany.

出版信息

Pathogens. 2023 Oct 30;12(11):1301. doi: 10.3390/pathogens12111301.

Abstract

Cardiac-targeted transgene delivery offers new treatment opportunities for cardiovascular diseases, which massively contribute to global mortality. Restricted gene transfer to cardiac tissue might protect extracardiac organs from potential side-effects. This could be mediated by using cis-regulatory elements, including promoters and enhancers that act on the transcriptional level. Here, we discuss examples of tissue-specific promoters for targeted transcription in myocytes, cardiomyocytes, and chamber-specific cardiomyocytes. Some promotors are induced at pathological states, suggesting a potential use as "induction-by-disease switches" in gene therapy. Recent developments have resulted in the identification of novel enhancer-elements that could further pave the way for future refinement of transcriptional targeting, for example, into the cardiac conduction system.

摘要

心脏靶向转基因递送为心血管疾病提供了新的治疗机会,心血管疾病是全球死亡的主要原因。将基因转移限制在心脏组织可能会保护心外器官免受潜在的副作用。这可以通过使用顺式调控元件来介导,包括作用于转录水平的启动子和增强子。在这里,我们讨论了用于在心肌细胞、心肌细胞和特定腔室心肌细胞中进行靶向转录的组织特异性启动子的例子。一些启动子在病理状态下被诱导,这表明它们有可能在基因治疗中用作“疾病诱导开关”。最近的进展导致了新型增强子元件的鉴定,这可能会为未来转录靶向的进一步优化铺平道路,例如进入心脏传导系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3519/10675517/392dfc7ca525/pathogens-12-01301-g001.jpg

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