US 12,422,437 B2
Methods of screening for condensate-associated specificity and uses thereof
Alexander Szewczak, Needham, MA (US); Ina Poser, Dresden (DE); Mark Andrew Murcko, Holliston, MA (US); Stephen Paul Hale, Belmont, MA (US); and Bruce Aaron Beutel, Needham, MA (US)
Assigned to Dewpoint Therapeutics, Inc., Boston, MA (US)
Filed by Dewpoint Therapeutics, Inc., Boston, MA (US)
Filed on Apr. 14, 2022, as Appl. No. 17/721,054.
Application 17/721,054 is a continuation of application No. 17/203,005, filed on Mar. 16, 2021, granted, now 11,340,231.
Application 17/203,005 is a continuation of application No. PCT/US2020/051331, filed on Sep. 17, 2020.
Claims priority of provisional application 62/902,316, filed on Sep. 18, 2019.
Prior Publication US 2022/0365093 A1, Nov. 17, 2022
Int. Cl. G01N 33/68 (2006.01); G01N 33/50 (2006.01); G01N 33/58 (2006.01); G01N 33/60 (2006.01)
CPC G01N 33/68 (2013.01) [G01N 33/5005 (2013.01); G01N 33/582 (2013.01); G01N 33/60 (2013.01); G01N 2496/00 (2013.01)] 27 Claims
 
1. A method of identifying a compound that preferentially affects a level of association of a macromolecule with a target condensate in a first cellular composition comprising a first cell of a first tissue type as compared to a level of association of the macromolecule with the target condensate in a second cellular composition comprising a second cell of a second tissue type,
wherein the target condensate in the first cellular composition and the second cellular composition are the same class of condensate,
the method comprising:
(a) contacting the first cellular composition with a compound, wherein:
(i) the first cell in the first cellular composition comprises the target condensate; and/or
(ii) the target condensate forms in the first cell in the first cellular composition simultaneously with and/or after contacting the first cellular composition with the compound;
(b) contacting the second cellular composition with the compound, wherein:
(i) the second cell in the second cellular composition comprises the target condensate; and/or
(ii) the target condensate forms in the second cell in the second cellular composition simultaneously with and/or after contacting the second cellular composition with the compound,
wherein the first cell of the first tissue type and the second cell of the second tissue type are of different tissue types;
(c) measuring the level of association of the macromolecule with the target condensate in the first cellular composition and the level of association of the macromolecule with the target condensate in the second cellular composition; and
(d) determining whether the compound preferentially affects the level of association of the macromolecule with the target condensate in the first cellular composition as compared to the level of association of the macromolecule with the target condensate in the second cellular composition,
wherein the determining is by comparing the level of association of the macromolecule with the target condensate in the first cellular composition relative to a reference level for the macromolecule associating with the target condensate in the first cellular composition and the level of association of the macromolecule with the target condensate in the second cellular composition relative to a reference level for the macromolecule associating with the target condensate in the second cellular composition,
wherein the compound preferentially affects the level of association of the macromolecule with the target condensate in the first cellular composition when the compound alters the level of association of the macromolecule as compared to the reference level for the macromolecule with the target condensate in the first cellular composition more than the compound alters the level of association of the macromolecule with the target condensate in the second cellular composition as compared to the reference level for the macromolecule with the target condensate in the second cellular composition, and
wherein the reference level for the macromolecule in the first cellular composition is the level of association of the macromolecule with the target condensate in the first cellular composition in the absence of the compound, and the reference level for the macromolecule in the second cellular composition is the level of association of the macromolecule with the target condensate in the second cellular composition in the absence of the compound.