LOCALIZED THERAPEUTICS LLC — Department of Health and Human Services SBIR Phase I: 101

Description

Optogenetic control over transgene expression for the therapy of brain and spine Abstract Gene modified stem cells are a powerful tool for the production of secretable therapeutic proteins in the body Yet there is a valid concern over their safety since there is no way to control them once they have been transplanted We propose to utilize optogenetic control of transcription ORT to externally control secretion of the therapeutic protein using red light ORT would improve the efficacy and safety of the therapy by repeated remote activation of transgene synthesis with red light delivered non invasively For a specific disease application we propose to use intrathecally delivered ORT driven stem cells to produce anti inflammatory anti TNF hybrid antibodies in the subarachnoid cavity for the therapy of neuroinflammation in the brain The ORT option would allow us to externally induce production of the anti inflammatory antibody using red light as needed At this initial phase of the project we propose the conceptual evaluation of the ORT system genetically embedded into bone marrow stem cells This testing is proposed in cell culture Aim and the mouse cerebral subarachnoid cavity Aim The proposed method aims to improve the safety and efficiency of the therapy of chronic CNS disorders with episodic neuroinflammatory components by providing the benefit of remote control of the timing and dosage of the therapy Narrative Gene modified stem cells offer promise for the therapy of central nervous disorders However the current methods of delivery and dosage adjustment are not sufficiently safe This proposal offers to test a novel concept of producing a biological drug in the subarachnoid cavity of the brain under repetitive induction by red light In this phase we propose to perform the initial evaluation of this technology in cell culture and a mouse model The option of control over gene modified cell activity would improve the efficacy and safety of central nervous system therapy opening new opportunities for treatment of brain and spinal cord disorders The proposed technology has the potential to facilitate the therapy s dosage adjustment and administration timing thus improving the quality of life and comfort of neuropsychiatric patients