Abstract: Novel 5? untranslated region (UTR)-targeting gene knock-in (KI) compositions and methods of use are disclosed. The gene KI compositions and methods exploit homology-independent targeted integration (HITI)-mediated insertion of a wild-type coding sequence (CDS) into the 5? UTR upstream of a translation initiation element of a mutated variant of the wild-type gene. The 5? UTR-targeting gene KI therapy compositions and methods provide safer and more efficient gene insertion compared to other gene therapy approaches.

Abstract: This invention relates to a treatment of various eye conditions relating to eye enlargement. The conditions can be treated by inhibiting an upstream protein within the said biological pathway or by increasing the expression of a downstream receptor within the same pathway. Inhibition of the upstream protein, sterol regulatory element binding protein (SREBP), has been achieved using small molecule inhibitors or nucleic acid in viral vector and increased expression of the downstream protein, bone morphogenetic protein (BMP), has been achieved by nucleic acid in viral vector. The invention relates to the small molecule, nucleic acid and the viral vector as well as methods of treating the ocular diseases.

Abstract: The present invention is directed to methods for the treatment or prevention of oxidative stress in a cell, e.g., photoreceptor cell, and methods for the treatment and prevention of disorders associated therewith by the administration of an agent, e.g., a nucleic acid molecule, which increases the expression and/or activity of an antioxidant defense protein.

Abstract: The present invention is directed to methods for the treatment or prevention of oxidative stress in a cell, e.g., photoreceptor cell, and methods for the treatment and prevention of disorders associated therewith by the administration of an agent, e.g., a nucleic acid molecule, which increases the expression and/or activity of an antioxidant defense protein.

Abstract: The present invention is directed to methods for the treatment or prevention of oxidative stress in a cell, e.g., photoreceptor cell, and methods for the treatment and prevention of disorders associated therewith by the administration of an agent, e.g., a nucleic acid molecule, which increases the expression and/or activity of an antioxidant defense protein.

Abstract: The present invention is based, at least in part, on the discovery that fragments of the histone deacetylase 4 (HDAC4) gene lacking the enzymatic domain promoted rod survival when electroporated into the retinas of a relevant mouse model of retinitis pigmentosa. Specifically, it has been discovered that only a small portion of the N-terminus of HDAC4 promotes survival of rod cells in rd1 mice. Accordingly, the present invention provides histone deacetylase 4 compositions and methods of use thereof for inhibiting neuronal cell death, e.g., retinal cell death.