Reagents for subcellular delivery of cargo to target cells
OwnerOmer ZIV, Andrej ALENDAR +1inventors
InventorsOmer ZIV, Andrej ALENDAR, Yaniv ERLICH
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Abstract
The present invention refers to a method for the separation/identification of reagents comprising a compound library, such as DNA-encoded Libraries (DELs), which enter target cells or localize to a desired subcellular compartment of said target cells, by amplifying and modifying the signal of a barcode attached to said reagents thereby significantly increasing the signal to noise ratio and distinguishing the reagents that successfully entered the desired cells or the desired subcellular compartment. Further disclosed herein are reagents, said reagent being able to enter a desired subcellular compartment of a target cell as well as therapeutic applications of said reagents.
Claims24
A method for generating and/or identifying a reagent, said reagent being able to enter a desired subcellular compartment of a target cell, comprising the following steps:
- a. preparing and/or selecting target cells comprising a polymerase localizing to said desired compartment;
- b. preparing a candidate library of reagents comprising or consisting of nucleic acid barcodes recognized by said polymerase;
- c. contacting said target cells with said library of reagents, wherein at least a subset of reagents interacts with at least a subset of target cells forming cell-reagent complexes;
- d. incubating the cell-reagent complexes thus obtained for a period of time at least sufficient to allow at least a subset of said reagents to enter a desired subcellular compartment of a target cell;
- e. amplifying the nucleic acid barcode of said subset of reagents of step d) by said polymerase of step a) within the desired subcellular compartment of the target cells and
- f. separating the amplified nucleic acid barcodes of step e) to generate and/or identify said reagent.
Dependencies are inferred from the claim text.