Compositions and methods for modulating molecules

The engineered polypeptide of any one of previous claims, wherein the first condensate is shifted to a second condensate when the engineered polypeptide is contacted with a third condensate modulator.

The engineered polypeptide of any one of previous claims, wherein the nuclear receptor or fragment thereof comprises an androgen receptor (AR) or a fragment thereof.

The engineered polypeptide of any one of previous claims, wherein the condensate shifting domain comprises at least one modification.

The engineered polypeptide of any one of previous claims, wherein the condensate shifting domain comprises at least one modification compared to any one of SEQ ID NOs:

• 1-10.

The engineered polypeptide of any one of previous claims, wherein the condensate modulator comprises a functional domain ligand.

The engineered polypeptide of any one of previous claims, wherein the condensate modulator comprises a nuclear receptor ligand.

The engineered polypeptide of any one of previous claims, wherein the engineered polypeptide forms the first condensate or the second condensate in cytoplasm of a cell.

The engineered polypeptide of any one of previous claims, wherein the engineered polypeptide forms the first condensate or the second condensate in cytoplasmic membrane of a cell.

The engineered polypeptide of any one of previous claims, wherein the functional domain comprises a kinase domain.

An engineered polynucleotide encoding the engineered polypeptide of any one of previous claims.

A cell comprising the engineered polypeptide or the engineered polynucleotide of any one of previous claims.

A pharmaceutical composition comprising the engineered polypeptide, the engineered polynucleotide, the cell, or the system of any one of previous claims.

A method of forming a first condensate in a cell, said method comprising contacting the cell with the engineered polypeptide, the engineered polynucleotide, or the system of any one of previous claims, wherein the first condensate is formed when the engineered polypeptide is operatively contacted with at least one other condensate shifting domain.

The method of any one of previous claims, wherein the first condensate is shifted to a second condensate when the engineered polypeptide is contacted with a third condensate modulator.

A method for increasing enzymatic activity in a cell, said method comprising contacting the engineered polypeptide or the engineered polynucleotide of any one of previous claims with a condensate modulator for forming a first condensate when the engineered polypeptide is operatively contacted with at least one other condensate shifting domain, wherein the first condensate enrich local enzyme concentration.

A method for increasing enzymatic activity in a cell, said method comprising contacting the engineered polypeptide or the engineered polynucleotide of any one of previous claims with a condensate modulator for forming a first condensate when the engineered polypeptide is operatively contacted with at least one other condensate shifting domain, wherein the first condensate brings two or more molecules of the enzymatic activity to close proximity, thereby increases enzymatic activity.

A method for modulating concentration of at least one molecule in a cell, said method comprising contacting the cell with the engineered polypeptide or the engineered polynucleotide of any one of previous claims, wherein a first condensate is formed when the engineered polypeptide, upon contacted with a condensate modulator, is operatively contacted with at least one other condensate shifting domain, wherein a concentration of the at least one molecule inside the first condensate is different to a concentration of the at least one molecule outside the first condensate.

A method for treating a disease or condition in a subject in need thereof, comprising administering the engineered polypeptide, the engineered polynucleotide, the cell, or the system of any one of previous claims to a subject.