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A minimal bile salt excretory pump promoter allows bile acid-driven physiological regulation of transgene expression from a gene therapy vector

Cell Biosci. 2022-05; 
Javier Martínez-García, Manuela Molina, Leticia Odriozola, Angie Molina, Gloria González-Aseguinolaza, Nicholas D Weber, Cristian Smerdou
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PCR Cloning and Subcloning … live mice at the indicated times (n = 3 for each gender except … 5end were ordered to Genscript and subcloned into pAAV-… end was also ordered to GenScript and subcloned into pAAV-… Get A Quote

摘要

background: Bile acid (BA) homeostasis is mainly regulated by bile salt excretory pump (BSEP), a hepatocyte transporter that transfers BAs to the bile. BSEP expression is regulated by BA levels through activation of farnesoid X receptor transcription factor, which binds to the inverted repeat (IR-1) element in the BSEP promoter. Gene therapy of cholestatic diseases could benefit from using vectors carrying endogenous promoters physiologically regulated by BAs, however their large size limits this approach, especially when using adeno-associated viral vector (AAV) vectors. results: We evaluated the functionality and BA-mediated regulation of minimal versions of human and mouse BSEP promoters containing IR-1 u... More

关键词

AAV, BSEP promoter, Bile acids, Cholestatic diseases, Gene therapy