The Johns Hopkins University

Derek Stuart Welsbie

Donald Jeffrey Zack

Zhiyong Yang

Justin Scot Hanes

Jie Fu

Cynthia Ann Berlinicke

Vinod Jaskula-Ranga

The presently disclosed subject matter provides compositions and methods comprising improvements of a CRISPR system (e.g. CRISPR associated (Cas) 9 (CRISPR-Cas9, non-Cas9 CRISPR systems). Such compositions may comprise modifications to the H1 promoter region, addition of 5'UTR modifications, different orthologous sequences of the H1 promoter, novel compact bidirectional promoter sequences with both pol II and pol III activity, addition of Kozak consensus sequences, termination sequences, addition of conditional pol II/pol III bidirectional promoter expression, addition of a donor template sequence for correcting mutations, or combinations thereof. Other aspects of the invention relate to modifications to Cas9 through post-transcriptional cell-cycle regulation fusions, engineered partial target sites such that the nuclease can bind without DNA cleavage, auto-regulation sites, and N-terminal modifications to modulate half-life.

Compositions and methods comprising improvements of CRISPR guide RNAS using the H1 promoter

Drug targets, pathways, kits and methods for treating conditions related to neurodegeneration or ocular disease, are disclosed.

Identification of molecular pathways and methods of use thereof for treating retinal neurodegeneration and other neurodegenerative disorders

Methods for increasing the encapsulation or incorporation of Sunitinib into polymeric matrices have been developed. The resulting formulations provide for more sustained controlled release of sunitinib or other inhibitors of JNK signaling, which bind to DLK. Increased loading is achieved using an alkaline solvent system. The pharmaceutical compositions can be administered to treat or reduce neuronal death due to elevated intraocular pressure. Upon administration, the sunitinib or other inhibitor is released over an extended period of time at concentrations which are high enough to produce therapeutic benefit, but low enough to avoid unacceptable levels of cytotoxicity, and which provide much longer release than inhibitor without conjugate.

Sunitinib formulations and methods for use thereof in treatment of glaucoma

Compounds, compositions, kits and methods for treating conditions related to neurodegeneration or ocular disease, are disclosed.

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Rancho Santa Fe, CA, United States of America

Derek Stuart Welsbie