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US 12,612,637 B2Granted
Compositions and methods for DHFR tunable protein regulation
AssigneeObsidian Therapeutics, Inc.
InventorsMara Christine Inniss, Janine Elizabeth Elya, Grace Y. Olinger, Vipin Suri
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Abstract
The present disclosure is related to compositions and methods for the regulated and controlled expression of proteins.
Claims27
A modified cell comprising:
- (a) a recombinant protein comprising an effector module, said effector module comprising a stimulus response element (SRE);
- and
- (b) at least one payload, said payload comprising a protein of interest which is attached, appended or associated with said SRE,
- wherein said SRE comprises a hDHFR mutant, wherein said hDHFR mutant comprises a Y122I mutation relative to SEQ ID NO.1 and further comprises one or two mutations selected from the group consisting of Q36E, Q36S, Q36T, Q36H, Q36R, K55R, N65K, N65L, N65R, N65H, N65W, Q103E, Q103S, Q103H, N108D, E162G, and K174N.
1 more element
An effector module comprising a hDHFR-derived SRE operably linked to a payload, wherein the hDHFR-derived SRE is a hDHFR mutant,
- said hDHFR mutant comprises the Y122I mutation relative to SEQ ID NO. 1 and further comprises one or two mutations selected from the group consisting of Q36E, Q36S, Q36T, Q36H, Q36R, K55R, N65K, N65L, N65R, N65H, N65W, Q103E, Q103S, Q103H, N108D, E162G, and K174N.
A nucleic acid molecule comprising a polynucleotide encoding a recombinant protein, said recombinant protein comprising a stimulus response element (SRE) linked to at least one payload;
- wherein the SRE comprises a destabilizing domain (DD), wherein said DD comprises a hDHFR mutant,
- said hDHFR mutant comprising a Y122I mutation relative to SEQ ID NO.1 and further comprising one or two mutations selected from the group consisting of Q36E, Q36S, Q36T, Q36H, Q36R, K55R, N65K, N65L, N65R, N65H, N65W, Q103E, Q103S, Q103H, N108D, E162G, and K174N, and wherein the SRE interacts with one or more stimuli.
Dependencies are inferred from the claim text.