Atrial-Specific Gene Delivery Using an Adeno-Associated Viral Vector

Abstract

Rationale: Somatic overexpression in mice using adeno-associated virus (AAV) as gene transfer vectors has become a valuable tool to analyze the roles of specific genes in cardiac diseases. The lack of atrial-specific AAV vector has been a major obstacle for studies into the pathogenesis of atrial diseases. Moreover, gene therapy studies for atrial fibrillation would benefit from atrialspecific vectors. Atrial natriuretic factor (ANF) promoter drives gene expression specifically in atrial cardiomyocytes. Objective: To establish the platform of atrial specific in vivo gene delivery by AAV-ANF. Methods and Results: We constructed AAV vectors based on serotype 9 (AAV9) that are driven by the atrial-specific ANF promoter. Hearts from mice injected with AAV9-ANF-GFP exhibited strong and atrial-specific GFP expression without notable GFP in ventricular tissue.

Junctophilin-2 expression rescues atrial dysfunction through polyadic junctional membrane complex biogenesis

“…AMs from MCM or MCMshJP2 hearts showed similar Ca 2+ transients ( Figure 6B) and there were no significant differences in the amplitude, time to peak, duration, or decay ( Figure 6C). Interestingly, whereas atrial junctophilin-2 knockdown via AAV9 gene transfer resulted in a decreased Ca 2+ transient amplitude and SR load 4 weeks after treatment (24), increased compensatory SERCA2a expression in our shJP2-knockdown model (Figure 4A) may preserve the Ca 2+ transient amplitude.…”

Recent progress in targeted delivery vectors based on biomimetic nanoparticles

“…A chronically infected rhesus monkey was functionally cured by continuous delivery of universally effective neutralizing monoclonal antibodies 3BNC117 and 10-1074 from a single dose administration of AAV vector. Ni et al 207 constructed a system of atrial-specific in vivo gene delivery using a recombinant AAV (rAAV) driven by the atrial-specific ANF promoter. Intriguingly, AAV with payloads can be ladened with phase-transition microneedles (MNs) for the therapy of ischemic myocardial disease via minimally invasive surgery 208 .…”

Imaging Techniques for the Study of Fibrosis in Atrial Fibrillation Ablation: From Molecular Mechanisms to Therapeutical Perspectives

“…New technologies, including integration between imaging and ECG and using artificial intelligence, are promising in this sense [ 69 ]; Complete understanding of the prevalent molecular pathway leading to atrial fibrosis. In fact, if, in the future, it becomes possible to identify each mechanism in each patient, new therapeutical techniques could be applied to develop a specific therapy targeting that pathway (i.e., genic therapy) [ 70 ]; Possible identification of a prevalent etiology of the AF (atrial fibrosis, circadian rhythm, ischaemia, autonomic imbalance, inflammation, and adiposity). Therefore, we have to manage all these factors together, without specificity.…”