Methods to spatially profile protease activity in tissue and sections
AssigneeMassachusetts Institute of Technology
InventorsSangeeta N. Bhatia, Jaideep S. Dudani, Ester J. Kwon, Andrew David Warren
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Abstract
Aspects of the disclosure relate to methods and compositions useful for in vivo and/or in vitro enzyme profiling. In some embodiments, the disclosure provides methods of in vivo enzymatic processing of exogenous molecules followed by detection of signature molecules as representative of the presence of active enzymes associated with diseases or conditions. In some embodiments, the disclosure provides compositions and in vitro methods for localization of enzymatic activity in a tissue sample.
Claims20
A pro-diagnostic reagent, the pro-diagnostic reagent comprising:
- (a) a carrier domain linked to a signature producing domain by a first linker molecule that comprises between 2 and 200 PEG molecules,
- wherein the signature producing domain comprises an enzyme susceptible domain linked to a signature molecule, wherein the enzyme susceptible domain is susceptible to cleavage by a protease, wherein the protease is upregulated in a cancer, and wherein cleavage of the enzyme susceptible domain by the protease releases the signature molecule, and
- (b) one or more tumor-penetrating peptides configured to bind to a receptor expressed by a cancer cell, wherein the receptor mediates an active transport pathway and wherein each tumor-penetrating peptide is linked to the carrier domain.
A pro-diagnostic reagent, the pro-diagnostic reagent comprising a carrier domain linked to a signature producing domain by a first linker molecule that comprises between 2 and 200 PEG molecules, wherein the signature producing domain comprises an enzyme susceptible domain linked to a signature molecule, wherein the enzyme susceptible domain is susceptible to cleavage by a protease, wherein the protease is upregulated in a cancer, and wherein cleavage of the enzyme susceptible domain by the protease releases the signature molecule.
Dependencies are inferred from the claim text.