Blocking phospholamban with VHH intrabodies enhances contractility and relaxation in heart failure.

ABSTRACT: The dysregulated physical interaction between two intracellular membrane proteins, the sarco/endoplasmic reticulum Ca²⁺ ATPase and its reversible inhibitor phospholamban, induces heart failure by inhibiting calcium cycling. While phospholamban is a bona-fide therapeutic target, approaches to selectively inhibit this protein remain elusive. Here, we report the in vivo application of intracellular acting antibodies (intrabodies), derived from the variable domain of camelid heavy-chain antibodies, to modulate the function of phospholamban. Using a synthetic VHH phage-display library, we identify intrabodies with high affinity and specificity for different conformational states of phospholamban. Rapid phenotypic screening, via modified mRNA transfection of primary cells and tissue,

SUBMITTER: De Genst E 

PROVIDER: S-EPMC9156741 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature