Engineering physiologically controlled pacemaker cells with lentiviral HCN4 gene transfer

Research on biological pacemakers for the heart has so far mainly focused on short‐term gene and cell therapies. To develop a clinically relevant biological pacemaker, long‐term function and incorporation of autonomic modulation are crucial. Lentiviral vectors can mediate long‐term gene expression, while isoform 4 of the Hyperpolarization‐activated Cyclic Nucleotide‐gated channel (encoded by HCN4) contributes to pacemaker function and responds maximally to cAMP, the second messenger in autonomic modulation.

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