TCAP adenovirus

The TCAP gene, also known as Titin-Cap or Telethonin, encodes a key structural protein in muscle sarcomeres. Located at the Z-disc of striated muscle fibers, TCAP interacts with titin, the largest known protein, thereby anchoring the sarcomere and maintaining its integrity during muscle contraction and relaxation. This protein acts as a molecular cap, stabilizing titin filaments and playing a crucial role in force transmission and mechanosensing. Mutations in the TCAP gene are associated with limb-girdle muscular dystrophy type 2G (LGMD2G), a rare autosomal recessive disorder characterized by progressive muscle weakness and atrophy. Studies have also shown that TCAP regulates muscle growth and differentiation by modulating signaling pathways such as the Akt/mTOR pathway.

TCAP adenoviral vectors are engineered tools in gene therapy and molecular research, designed to deliver the TCAP gene into target cells. These replication-deficient adenoviruses carry TCAP cDNA under the control of a promoter, enabling efficient transduction of muscle cells in vitro and in vivo. In preclinical studies, TCAP adenoviruses have been used to rescue muscle function in LGMD2G animal models by restoring sarcomere stability and improving force generation. Beyond disease correction, these vectors also facilitate the study of TCAP's mechanisms in muscle hypertrophy, atrophy, and mechanotransduction. For example, adenoviral overexpression has revealed that TCAP can inhibit muscle atrophy pathways such as ubiquitin-proteasome activation.