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METHOD TO GENERATE ACTIVE SINGLE-CHAIN GPCR-G-PROTEIN ALPHA COMPLEX

The inventor has created a method to engineer a single polypeptide chain of a protein complex containing a G-protein coupling receptor (GPCR) and a G-protein alpha subunit (SPC-GPCR-Ga), which could regulate and reverse ligand (drug) functions. For example, endogenous thromboxane A2 (TXA2) and its agonist drugs bind to its GPCR (TP) coupled to G-protein q mediating calcium signaling. Acting together, these regulators mediate platelet aggregation, blood clotting and vasoconstriction, all of which are directly involved in causing of heart diseases (such as, pulmonary arterial hypertension, stroke, restenosis and heart arrest). The invention has created a SPC-GPCR-Ga to reverse the TXA2 and its agonists’ functions by converting calcium signaling to cAMP signaling, which could inhibit platelet aggregation, prevent bleed clot and dilate blood vessels. Using of the inverted cDNA of SPC-GPCR-Ga transfecting cells, tissues and arteries could be a novel and advance therapeutic intervention for the high mortality diseases, pulmonary arterial hypertension, stroke, restenosis and heart arrest.

Applications

Treatment of:

  • Restenosis
  • Pulmonary Arterial Hypertension
  • Post Stem Vascular Protection
  • Coronary artery diseases
  • Thrombosis

Problems Addressed

  • Using multifunctional fusion protein of GPCR-G protein complex through gene therapy to treat high-mortality diseases, such as vascular restenosis, pulmonary arterial hypertension and other thrombotic cardiovascular diseases.

Competitive Advantages

  • Long lasting therapeutic
  • Suitable for local gene therapy
  • Less toxic

Patents

  • US Patent No.62/662,913