Biological pacemakers including mutated hyperpolarization-activated cyclic nucleotide-gated (HCN) channels
AssigneeMedtronic, Inc.
InventorsDaniel C. Sigg, Vinod Sharma, Yong-Fu Xiao
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Abstract
A composition for implantation into cardiac tissue includes a biological pacemaker that, when implanted, expresses an effective amount of a mutated hyperpolarization-activated and cyclic nucleotide-gated (HCN) isoform to modify Ih when compared with wild-type HCN. Methods for implementing each of the biologocal pacemakers include implanting each of biologocal pacemakers into cardiac tissue.
Claims40
A composition for implantation into cardiac tissue, comprising a biological pacemaker comprising a polynucleotide sequence encoding a mutated hyperpolarization-activated and cyclic nucleotide-gated (HCN) isoform that, when implanted, expresses an effective amount of the mutated HCN isoform to modify Ih activation kinetics, wherein the HCN isoform is HCN-4, the mutation comprises a S3-S4 linker mutation, and the mutated HCN-4 demonstrates increased Ih activation kinetics compared to wild type HCN-4.
A composition for implantation into cardiac tissue, comprising a biologocal pacemaker comprising a polynucleotide sequence encoding a mutated hyperpolarization-activated and cyclic nucleotide-gated (HCN) isoform that, when implanted, expresses an effective amount of the mutated HCN isoform to modify Ih activation kinetics, wherein the HCN isoform is HCN-4 and the mutation comprises a S3-S4 linker mutation and wherein the mutated HCN-4 demonstrates increased Ih activation kinetics compared to wild type HCN-4 and demonstrates V1/2 kinetics that are unchanged compared to wild type HCN-4.
A composition for implantation into cardiac tissue comprising a polynucleotide sequence encoding a mutated hyperpolarization-activated and cyclic nucleotide-gated-4 (HCN-4) isoform, wherein the mutated HCN-4 comprises a S3-S4 linker mutation selected from the group consisting of T360A, T360A+Δ363-367, TRI360-362KGM, and TRI360-362AGM+Δ363-367.
An isolated polynucleotide sequence that encodes a mutated HCN-4 comprising a S3-S4 linker mutation selected from the group consisting of T360A, T360A+Δ363-367, TRI360-362KGM, and TRI360-362AGM +66 363-367.
Dependencies are inferred from the claim text.