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

Description

DESCRIPTION provided by applicant Infrared activated promoter for gene therapy of arthritis It is fair to generalize that unfortunately more patients currently die from toxicity of medications than from disease Although gene therapy is a promising alternative to small molecule drugs allowing to produce biologics inside the body and to reduce costs of treatment its progress has been stalled due to the lack of a means of control over the transgene activity Since transgenes are active in the body for a long time current gene therapy lacks safety Effective control over transgene activity would offer safety and improve efficacy We have identified a promoter sequence which is indirectly activated by infrared light and propose to use it to control transgenes in gene therapy Here we propose to optimize near infrared promoter activation in cell culture by optimizing the promoter sequence and irradiation parameters and test the optimized near infrared promoter in mice This project will serve as a proof of principle for the feasibility of near infrared light inducible gene therapy Addition o this means of control will allow making gene therapy safer by keeping transgenes dormant most of the time and activating them with non burning infrared irradiation when needed thus effectively replacing small molecule medications with repeated light treatments This will allow to reduce toxicity and side effects in arthritis therapy as well as to localize therapy only to select joints thus sparing the body from the systemic adverse side effects PUBLIC HEALTH RELEVANCE It is fair to generalize that unfortunately more patients currently die from toxicity of pharmaceuticals than from disease Gene therapy is a promising alternative to conventional drugs Despite isolated successes its progress has been stalled due to a lack of control over drug activity Since DNA based drugs are active in the body for a long time current gene therapy lacks safety Effective control over transgene activity would offer safety and improve its efficiency In this study we propose proof of principle experiments for the creation and use of light inducible gene therapy The addition of light as a means of control will allow us to make gene therapy safer keeping DNA based drugs dormant most of the time and activating them with non burning light irradiation repeatedly when needed By replacing toxic small molecule medications with repeated light treatments we intend to reduce toxicity and side effects in arthritis therapy as well localize the therapy to selected joints thus sparing the bod from systemic side effects