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Published on: September 27, 2013
Lesion-targeted injectable vectors for vascular restenosis
E M Gordon1, N L Zhu, M Forney Prescott
1Gene Therapy Laboratories, Keck School of Medicine of the University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA.
Human Gene Therapy
|July 7, 2001
Summary
Targeted retroviral vectors effectively deliver gene therapy to vascular injury sites. This approach shows promise for treating restenosis by inhibiting neointima formation.
Area of Science:
- Cardiovascular Gene Therapy
- Vascular Biology
- Biotechnology
Background:
- Catheter-based revascularization can cause vascular injury, leading to neointima formation and restenosis.
- Extracellular matrix (ECM) proteins and collagen deposition are key features of vascular lesions.
- Retroviral vectors have been engineered to target matrix-collagen for enhanced localization.
Purpose of the Study:
- To evaluate the efficiency of matrix-collagen-targeted retroviral vectors in targeting vascular lesions.
- To assess the therapeutic potential of these vectors in inhibiting neointima formation in a rat carotid artery injury model.
Main Methods:
- Development of matrix-collagen-targeted retroviral vectors using a von Willebrand factor-derived motif.
- Administration of targeted and non-targeted vectors via intraarterial and intravenous routes in balloon-injured rat carotid arteries.
- Quantification of neointimal cell transduction and assessment of neointima lesion formation.
Main Results:
- Matrix-targeted vectors significantly enhanced transduction of neointimal cells (approx. 20%) compared to non-targeted vectors (<1%).
- Intraarterial delivery of a targeted vector carrying an antisense cyclin G1 construct inhibited neointima lesion formation.
- Non-targeted vectors did not show significant inhibition of neointima formation.
Conclusions:
- Strategic targeting of retroviral vectors to vascular lesions is efficient in concentrating therapeutic agents at sites of injury.
- This vector-targeting system holds therapeutic potential for managing vascular restenosis.
- The approach may be applicable to other disorders characterized by endothelial disruption, ECM remodeling, and collagen deposition.
