# Regional Gene Therapy to Enhance Bone Repair

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $402,803

## Abstract

Project Summary
The goal of this proposal is to assess the bone repair potential of human bone marrow cells
transduced with a lentiviral vector containing the cDNA for BMP-2. There are a number of
difficult bone repair scenarios for which there is no consistently satisfactory solution including:
fracture nonunion, acute fractures with extensive bone loss, revision total joint arthroplasty and
pseudarthrosis of the spine. Traditionally, autologous bone graft has been the gold standard but
there is a limited supply of this bone and there are concerns regarding the morbidity associated
with graft harvest. Recombinant bone morphogenetic proteins (BMP) are FDA approved for use
in spinal fusion and treatment of fresh tibial fractures. However, BMPs have had mixed success
in humans and are associated with side effects including soft tissue edema and heterotopic
ossification. Orthopaedic surgeons have been searching for alternative tissue engineering
strategies to enhance bone repair. Our plan is to develop regional gene therapy using
transduced bone marrow cells as one aspect of a comprehensive tissue engineering strategy to
enhance bone repair.
It has been demonstrated in animal models that gene therapy with BMP producing bone marrow
cells created via lentiviral gene transfer has the potential to treat either medium or large bone
defects or when the biological environment of the host is severely compromised. In this proposal
we plan to test our hypothesis that human bone marrow cells transduced with a lentiviral vector
to overexpress BMP-2 have the potential to enhance bone repair in humans. Human bone
marrow cells will be harvested from the intramedullary canals of patients undergoing total hip
arthroplasty. The cells will be transduced with a lentiviral vector (LV-TSTA-iC9/BMP-2) that
contains the cDNA for BMP-2 and an inducible suicide gene (iCaspase 9) and then implanted
in a critical sized femoral defect model in nude rats. We propose the following aims to
accomplish the goal including: 1) compare the efficacy of regional gene therapy after bone
repair with freshly isolated or cultured expanded human bone marrow cells; 2) establish a
“cellular dose” of transduced cells that can be scaled up for use in humans; and 3) determine
the local and systemic biodistribution of BMP transduced human cells and assess for organ
toxicity, vector genotoxicity and heterotopic ossification. The data obtained from this proposal
will provide critical information with respect to adapting this regional gene therapy strategy as a
treatment regimen in humans.

## Key facts

- **NIH application ID:** 10137784
- **Project number:** 5R01AR057076-10
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** JAY R. LIEBERMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $402,803
- **Award type:** 5
- **Project period:** 2010-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137784

## Citation

> US National Institutes of Health, RePORTER application 10137784, Regional Gene Therapy to Enhance Bone Repair (5R01AR057076-10). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10137784. Licensed CC0.

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