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Tailored Gene Therapeutic Strategies for Peripheral Vascular Disease (PVD)

University of New South Wales

Grant:
  • Cardiovascular Senior Researcher Grant
Date Funded:
  • 1 February, 2022
Chief Investigator/s:
  • Professor Levon Khachigian

Project Summary

Tailored Gene Therapeutic Strategies for Peripheral Vascular Disease (PVD).

The main researcher for this project is Professor Levon Khachigian.

What is the issue for NSW?

The prevalence of PVD is increasing globally with 1 in 5 Australians affected.  PVD carries a poor prognosis, reduced life expectancy and risk of amputation. Of PVD patients in NSW hospitals, 34% of patients discharged experienced at least one complication while 35% of patients were re-admitted to hospital within 1 month of leaving hospital.

PVD requires endovascular repair (i.e. mending inside the blood vessel) with drug-coated stents or balloons or bypass grafting of narrowed arteries. However, graft failure and restenosis (i.e. re-narrowing of the blood vessel) in PVD is observed in 30-40% of patients within 2 years due to re-occlusion and blood clots (thrombosis), pathologic features of failed haemodialysis arteriovenous fistulae where overall primary patency rate at 2 years is only 55%. Re-occlusion and thrombosis can occur because cells called smooth muscle cells (SMC) grow aggressively while endothelial cells (EC) grow poorly.

What does the research aim to do and how?

This project aims to develop a novel cell selective gene therapeutic (YY1B) to prevent complications in PVD treatment (post-intervention restenosis, graft stenosis and fistula failure) using tailored AAV selection strategies bringing together world leaders in gene therapy, PVD and translational research.

There are four aims: first, construct and test novel viral constructs of YY1B with vascular cells and human veins; second, to investigate the protective of viral YY1B in animal models of graft stenosis; third, determine the inhibitory effects of viral YY1B in a diabetic model of in-stent restenosis; and finally, to understand in greater detail how YY1B works.