Disclosed herein include methods, compositions, and kits suitable for use in detecting the activation level of a signal transducer. In some embodiments, there are provided synthetic protein circuits wherein recruitment of synthetic protein circuit components to an association location upon activation of a signal transducer generates an active effector protein. The effector protein can be configured to carry out a variety of functions when in an active state, such as, for example, inducing cell death. Methods of treating a disease or disorder characterized by aberrant signaling are provided in some embodiments.

The invention relates to fusion polypeptides, nucleic acid molecules encoding said fusion polypeptides and genetically modified cells including said nucleic acid molecules. Moreover, the invention relates to a method for preparing target polypeptides using the fusion polypeptides.

The disclosure provides compounds of formula II with warheads and their use in treating medical diseases or disorders, such as viral infections. Pharmaceutical compositions and methods of making various compounds with warheads are provided. The compounds are contemplated to inhibit proteases, such as the 3C, CL- or 3CL-like protease.

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The present invention relates to enzyme inhibitors. More specifically, the present invention relates to ligand-directed covalent modification of proteins; method of designing same; pharmaceutical formulation of same; and method of use.

Disclosed herein include methods, compositions, and kits suitable for use in detecting the activation level of a signal transducer. In some embodiments, there are provided synthetic protein circuits wherein recruitment of synthetic protein circuit components to an association location upon activation of a signal transducer generates an active effector protein. The effector protein can be configured to carry out a variety of functions when in an active state, such as, for example, inducing cell death. Methods of treating a disease or disorder characterized by aberrant signaling are provided in some embodiments.

The subject invention pertains to a chimeric antigen receptor, a T cell comprising said CAR and methods of making and using said CAR and said T cell for the treatment of a cancer and/or an immune disease. In specific embodiments, the method comprises the use of T cells comprising CARs to target different antigens on target cells. In further specific embodiments, the CARs of the invention comprise NS3 protease domains and cleavage sites, which NS3 domains are inhibited by small molecule inhibitors for customized CAR-T cell therapy.

The technology described herein is directed to regulated synthetic gene expression systems. In one aspect described herein are synthetic transcription factors (synTFs) comprising a DNA binding domain, a transcriptional effector domain, and a regulator protein. In other aspects described herein are gene expression systems comprising said synTFs and methods of treating diseases and disorders using said synTFs.

Provided herein are non-naturally occurring self-assembling polypeptides for transferring nucleic acids and/or proteins to a cell, pharmaceutical compositions comprising such polypeptides, and methods for treatment comprising use of such compositions. The methods for producing polypeptide compositions may include combining in a solution, unassembled recombinant GAG-like proteins, nucleic acids and/or proteins in low salt conditions; and increasing the ionic strength of the solution.

The present invention relates to synthetic α-secretase (SAS) and a use thereof. According to the present invention, a synthetic α-secretase, which is a fusion protein comprising, as an active ingredient, NIa protease, a fragment thereof or a variant thereof, can inhibit the formation of amyloid β, degrade extracellularly secreted amyloid β, and degrade amyloid β internalized in cells. Therefore, the present invention allows intracellular/extracellular degradation of amyloid β, which is the cause of various diseases including Alzheimer's disease, and thus can be usable in the prevention or treatment of such diseases.

Provided are fusion proteins and related molecules useful for conducting base editing with reduced or no off-target mutations. The fusion protein may include a first fragment comprising a nucleobase deaminase or a catalytic domain thereof, a second fragment comprising a nucleobase deaminase inhibitor, and a protease cleavage site between the first fragment and the second fragment. Also provided are improved prime editing systems, including prime editing guide RNA with improved stability.