Methods and compositions using genetic package display

A method of identifying a target cell or tissue for a ligand, comprising:

• (a) contacting a ligand displaying genetic package comprising an in-frame insert with a cell(s) or tissue(s), wherein the package comprises a nucleic acid sequence encoding a detectable product;
• and
• (b) detecting product in the cell(s) or tissue(s), and thereby identifying a target cell or tissue for an internalizing ligand.

A method of selecting an internalizing ligand displayed on a genetic package, comprising:

• (a) contacting a library of ligand displaying genetic packages comprising in-frame inserts with a cell(s), wherein each package comprises a nucleic acid sequence encoding a detectable product, and
• (b) detecting product in the cell(s);
• and thereby selecting an internalizing ligand displayed on a genetic package.

A method of selecting internalizing ligand/anti-ligand pairs, comprising:

• (a) contacting a library of ligand displaying genetic packages comprising in-frame inserts with a cell(s), wherein each package comprises a nucleic acid sequence encoding a detectable product, and wherein the cell(s) expresses an anti-ligand-receptor fusion protein on its surface;
• and
• (b) detecting product expressed by the cell(s), and thereby selecting internalizing ligand/anti-ligand pairs.

A method of identifying a target cell or tissue for an internalizing ligands, comprising:

• (a) contacting a ligand displaying genetic package comprising a nucleic acid sequence encoding a detectable mRNA that is expressed upon internalization of the package with a cell(s) or a tissue(s);
• and
• (b) detecting the detectable mRNA expressed by the cell(s) or tissue(s), and thereby identifying a target cell or tissue for internalizing ligands.

A method of selecting an internalizing ligand displayed on a genetic package, comprising:

• (a) contacting a library of ligand displaying genetic packages comprising a nucleic acid sequence encoding a detectable mRNA that is expressed upon internalization of the package with a cell(s), and
• (b) detecting the detectable mRNA expressed by the cell(s);
• and thereby selecting an internalizing ligand displayed on a genetic package.

A method of selecting internalizing ligand/anti-ligand pairs, comprising:

• (a) contacting a library of ligand displaying genetic packages comprising a nucleic acid sequence encoding a detectable mRNA that is expressed upon internalization of the package with a cell(s) that expresses an anti-ligand-receptor fusion protein on its surface;
• and
• (b) detecting the detectable mRNA expressed by the cell(s), and thereby selecting internalizing ligand/anti-ligand pairs.

A method of identifying a target cell or tissue for an internalizing ligand, comprising:

• (a) contacting a ligand displaying genetic package comprising a detectable DNA with a cell(s) or a tissue(s);
• and
• (b) detecting the detectable DNA in the cell(s) or tissue(s), and thereby identifying a target cell or tissue for internalizing ligands.

A method of selecting an internalizing ligand displayed on a genetic package, comprising:

• (a) contacting a library of ligand displaying genetic packages comprising a detectable DNA with a cell(s), and
• (b) detecting the detectable DNA in the cell(s);
• and thereby selecting an internalizing ligand displayed on a genetic package.

A method of selecting internalizing ligand/anti-ligand pairs, comprising:

• (a) contacting a library of ligand displaying genetic packages comprising a detectable DNA with a cell(s) that expresses an anti-ligand-receptor fusion protein on its surface;
• and
• (b) detecting the detectable DNA in the cell(s), and thereby selecting internalizing ligand/anti-ligand pairs.

A method of identifying a target cell or tissue for an internalizing ligand, comprising:

• (a) contacting a ligand displaying genetic packages comprising a nucleic acid sequence encoding a detectable product with a cell(s) or tissue(s), wherein the nucleic acid sequence comprises an intron;
• and
• (b) detecting products expressed by the cell(s) or tissue(s), and thereby identifying a target cell or tissue for an internalizing ligand.

A method of selecting internalizing ligand/anti-ligand pairs, comprising:

• (a) contacting a library of ligand displaying genetic packages comprising a nucleic acid sequence encoding a detectable product with a cell(s), wherein the nucleic acid sequence comprises an intron, and wherein the cell(s) expresses an anti-ligand-receptor fusion protein on its surface;
• and
• (b) detecting product expressed by the cell(s), and thereby selecting internalizing ligand/anti-ligand pairs.

A method of identifying an internalizing ligand and/or an anti-ligand of a ligand/anti-ligand pair, comprising the method of claim 209 and further comprising recovering a nucleic acid molecule encoding an internalizing ligand and/or a nucleic acid molecule encoding an internalizing anti-ligand from cell(s) that express the detectable product, and thereby identifying a ligand and/or anti-ligand of an internalizing ligand/anti-ligand pair.