Provided herein is an in-series synthetic receptor circuit for dual-antigen AND-gate control over expression of a therapeutic payload by engineered cells. In some embodiments, the circuit may be composed of a first binding-triggered transcriptional switch, a second binding-triggered transcriptional switch and a therapeutic payload (e.g., a chimeric antigen receptor), where binding of the first binding-triggered transcriptional switch to a first antigen activates expression of the second binding-triggered transcriptional switch, and binding of the second binding-triggered transcriptional switch to a second antigen activates expression of the therapeutic payload. If the cell is an immune cell and the therapeutic payload is a chimeric antigen receptor, then the immune cell may be activated by binding of the chimeric antigen receptor to a third antigen. Methods of treatment using the cell also provided.

Disclosed herein are modified strains for improving secretion of recombinantly expressed products secreted from a host organism with improved growth and productivity characteristics, as well as methods of using the modified strains.

The present invention relates to binding fusion protein compositions comprising targeting moieties linked to extended recombinant polypeptide (XTEN), binding fusion protein-drug conjugate compositions, and XTEN-drug conjugate compositions, isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of using such compositions in treatment of diseases, disorders, and conditions.

Disclosed herein are cells including pluripotent stem cells that conditionally express an immunosuppressive factor and related methods of their use and generation. In some embodiments, the cells disclosed do not express MHC I and MHC II human leukocyte antigens, and in some cases, also do not express one or more TCR complexes. In some embodiments, hypoimmunogenicity of the cells is controlled by activation of a controllable expression system upon contacting the cells with a specific factor or agent.

Methods of preventing or treating autoimmune disease are disclosed. In some cases, subjects with having or at risk of developing autoimmune disease are identified as possessing one or more autoimmunity-susceptibility HLA alleles at one or more HLA loci. In many cases, the HLA loci are selected from Class I and Class II loci, for example Class I A, B, and C, and Class II DQ, DR, and DP. In many cases, subjects suffering from or at risk of developing an autoimmune disease may be administered a plurality engineered autologous HSCs modified to carry and express a variant susceptibility allele having at least one mutation in the antigen binding cleft that alters antigen binding and/or specificity of that variant HLA molecule. In many embodiments, the engineered HSCs are CD34+ immune cells that express one or more modified HLA proteins.

Tobacco etch virus protease (TEV) is one of the most widely used proteases in biotechnology because of its exquisite sequence-specificity. A limitation of TEV is its slow catalytic rate, which limits product generation and therefore signal output. Provided is a generalizable yeast-based platform for directed evolution of protease catalytic properties. Protease activity is determined via proteolytic release of a membrane-anchored transcription factor, and access to TEV's cleavage site is temporally regulated using a photosensory LOV domain. By gradually decreasing light exposure time, faster variants of TEV were selected over multiple rounds of selection. The mutant TEV proteases and the directed evolution platform are useful in a wide range of biotechnology applications, such as FLARE and SPARK tools.

The present invention relates to multispecific transthyretin (TTR) complexes useful as multispecific binding proteins. The multispecific TTR complexes described herein are particularly useful in binding to one, two, or more epitopes which may be present on one or more proteins. Methods for treating diseases using the TTR complexes of the present invention are described herein.

Provided is a novel cancer gene therapeutic means. More specifically, provided is a nucleic acid having a structure in which (A) a nucleic acid encoding a protein having a CD44 extracellular function, (B) a nucleic acid encoding a protein having a Notch core region function, and (C) a nucleic acid encoding a protein having an HIF-3α4 function are linked in the order of (A)-(B)-(C).

The present disclosure provides improved CLL-1 targeting polypeptides and compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

The present disclosure provides dimeric antigen receptors (DAR) constructs that bind a CD20 target antigen, where the DAR construct comprises a heavy chain binding region on one polypeptide chain and a light chain binding region on a separate polypeptide chain. The two polypeptide chains that make up the dimeric antigen receptors can dimerize to form an antigen binding domain. The dimeric antigen receptors have antibody-like properties as they bind specifically to a target antigen. The dimeric antigen receptors can be used for directed cell therapy.