Methods for profiling extracellular vesicles from combinatorial phage display libraries

Abstract

A method for profiling extracellular vesicles (EV) is provided. The method includes: (a) incubating isolated EV from one or more sources with a phage display library under conditions suitable for forming EV-bound phage, wherein the phage display library comprises one or more types of phage, each type of phage having a displayed proteinaceous display binding moieties capable of recognizing one or more epitopes on the surface of the EV, wherein each type of phage comprises nucleic acids encoding the displayed proteinaceous display binding moieties, and wherein the displayed proteinaceous display binding moieties of each type of phage is different; (b) isolating the EV-bound phage; (c) extracting the nucleic acids from the EV-bound phage; (d) amplifying the extracted nucleic acids; (e) sequencing the amplified nucleic acids to identify specific nucleic acid sequences associated with each type of phage from the library that are enriched from the isolated EV; and (f) comparing the specific nucleic acid sequences (output) with nucleic acid sequences from the phage display library (input) and nucleic acid sequences from a control to identify sequences that can distinguish between EV from the one or more sources.