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US 11,427,861 B2Granted
Methods for identifying and modulating co-occurant cellular phenotypes
AssigneeMassachusetts Institute of Technology
InventorsAlexander K. Shalek, Alexander S. Genshaft, Carly G. K. Ziegler, Jeffrey F. Van Humbeck
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Abstract
The present invention provides tools and methods for the systematic analysis of genetic interactions between cells. The present invention provides tools and methods for modulating cell phenotypes and compositions, combinatorial probing of cellular circuits, for dissecting cellular circuitry, for delineating molecular pathways, and/or for identifying relevant targets for therapeutics development.
Claims11
A cell functionalizing probe comprising:
- (a) a polyadorned molecule comprising 3 to 5 substituents, comprising;
- (i) a first photoactivated cell-surface reactive group comprising a diazirine or a benzophenone;
- (ii) a first bio-orthogonal reactive group comprising a compound of Formula (I):
- wherein R1 is selected from the group consisting of —H, —X, —(CH2)a—NH-PG1, O—(CH2CH2O)a(CH2)cNH2—PG1, O—(CH2CH2O)a—PG2, —(CH2)a—O-PG2;
- R2 is selected from the group consisting of —C(O)(CH2)aCO2R21, —CO2(CH2CH2O)aCO2R21, —C(O)(CH2)aCONR21, —CO2(CH2CH2O)aCONR21, and —CO(CH2)aNHCO(CH2)aO(CH2CH2O)c(CH2)aNHR21;
- R21 is selected from the group consisting of —H, —O(C1-C6 alkyl), —C1-C8 straight chain alkyl, —C1-C8 branched alkyl, —C2-C8 alkenyl, —C2-C8 alkynyl and —(C1-C6 alkyl)-O—(C1-C6 alkyl);
- PG1 is an amine protecting group or —H;
- PG2 is an alcohol protecting group or —H;
- and
- X is selected from the group consisting of Cl, Br, I, and F;
- a is independently any integer between 0 and 6;
- c is independently any integer between 1 and 6;
- and
- the additional substituents are individually selected from a label, a cell-surface reactive group, or a bio-orthogonal reactive group, and wherein when the photoactivated cell-surface reactive group comprises benzophenone, the polyadorned molecule comprises phenyl, naphthyl, anthracenyl, phenanthrenyl, indanyl, indenyl, dihydroxyaryl or triazine.
11 more elements
Dependencies are inferred from the claim text.