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Articles by Luzi Yang
An all-in-one AAV vector for cardiac-specific gene silencing by an adenine base editor
Abstract ABE editing outcomes are highly variable and unpredictable, depending on various factors. Therefore, the success rate of creating targeted AT-to-GC conversions using ABE is not high. But utilizing ABE to target RNA splicing sites for gene silencing has a higher success rate. Another challenge for base editing in the heart is that traditional ABE is too large in size, necessitating dual AAV delivery. Whether single AAV delivery can be achieved remains to be explored.
A Drug-Elicitable Alternative-Splicing Module (DreAM) for Tunable AAV Expression and Controlled Myocardial Regeneration
Abstract Adeno-associated virus (AAV) is a major vector for gene therapy. A technique to fine-tune the time and level of AAV expression is lacking, which greatly restricts indication choice, therapeutic efficacy and safety. To solve this problem, here we developed a drug-elicitable alternative-splicing module (DreAM) responsive to risdiplam, an FDA-approved alternative splicing modulator.
Myocardial infarction creates a critical time window for AAV gene therapy
Abstract Recombinant adeno-associated virus (AAV) is a major gene delivery vector for cardiac gene therapy. The factors that influence AAV-based cardiac gene transfer remain incompletely understood. This study showed that myocardial infarction (MI) enhanced cardiac AAV transduction and gene expression in mice after systemic administration, peaking at the third day post MI.
Adenine base editor‐based correction of the cardiac pathogenic Lmna c.1621C > T mutation in murine hearts
1 INTRODUCTION Single-nucleotide variation (SNV) is a major form of genetic aberrations that can cause or modify human diseases. Nearly half of pathogenic SNVs are C•G-to-T•A base pair conversions, which can potentially be corrected by the adenine base editors (ABE).1 ABEs are ribonucleoprotein complexes that are composed of a single-guide RNA (sgRNA) and a TadA-Cas9n fusion protein.
MicroRNA-122-mediated liver detargeting enhances the tissue specificity of cardiac genome editing
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