Engineered transcription factors for therapeutic angiogenesis

Angiogenesis is defined as the growth and proliferation of blood vessels from existing vascular structures. Therapeutic angiogenesis seeks to harness the mechanisms of vascular growth to treat disorders of inadequate tissue perfusion. Early clinical trials of therapeutic angiogenesis met with limited success, in part due to the complex spatial and temporal regulation of angiogenesis, which requires the coordinate action of multiple growth factors and their receptors. Engineered transcription factors represent a novel and innovative approach to modulate this process as they offer the ability to induce expression of multiple angiogenic genes simultaneously. The rational design of these transcription factor agents, results of their use in preclinical models of ischemic disease and prospects for their use in human investigations are discussed in this review.