Provided are methods and compositions for generating a deletion library, and methods and compositions for generating and identifying a defective interfering particle (DIP). Also provided are transposon cassettes. A subject method can include: inserting a transposon cassette comprising a target sequence for a sequence specific DNA endonuclease into a population of circular target DNAs to generate a population of transposon-inserted circular target DNAs; contacting the population of transposon-inserted circular target DNAs with the sequence specific DNA endonuclease to generate a population of cleaved linear target DNAs; contacting the population of cleaved linear target DNAs with one or more exonucleases to generate a population of deletion DNAs; and circularizing the deletion DNAs to generate a library of circularized deletion DNAs. The population of circular target DNAs can include viral genomic DNA. Also provided are human immunodeficiency virus (HIV) deletion mutants, e.g., interfering, conditionally replicating, HIV deletion mutants, and related constructs.

Provided are methods and compositions for generating a deletion library, and methods and compositions for generating and identifying a defective interfering particle (DIP). Also provided are transposon cassettes. A subject method can include: inserting a transposon cassette comprising a target sequence for a sequence specific DNA endonuclease into a population of circular target DNAs to generate a population of transposon-inserted circular target DNAs; contacting the population of transposon-inserted circular target DNAs with the sequence specific DNA endonuclease to generate a population of cleaved linear target DNAs; contacting the population of cleaved linear target DNAs with one or more exonucleases to generate a population of deletion DNAs; and circularizing the deletion DNAs to generate a library of circularized deletion DNAs. The population of circular target DNAs can include viral genomic DNA. Also provided are human immunodeficiency virus (HIV) deletion mutants, e.g., interfering, conditionally replicating, HIV deletion mutants, and related constructs.

Provided is a method for producing an artificial recombinant RNA virus stably expressing a foreign gene, comprising the steps of: (1) obtaining a foreign gene having a modified codon composition similar to that of an RNA virus gene; (2) inserting the foreign gene obtained in step (1) into an RNA virus genome; and (3) artificially synthesizing an artificial recombinant RNA virus using reverse genetics.

Provided is a method for producing an artificial recombinant RNA virus stably expressing a foreign gene, comprising the steps of: (1) obtaining a foreign gene having a modified codon composition similar to that of an RNA virus gene; (2) inserting the foreign gene obtained in step (1) into an RNA virus genome; and (3) artificially synthesizing an artificial recombinant RNA virus using reverse genetics.

Provided is a MART-1 (27-35) epitope-specific T cell receptor, comprising an α chain and a β chain. The α chain comprises three complementary determining regions, respective sequences thereof being positions 61-66, positions 84-89, and positions 124-136 of SEQ ID No. 3. The β chain comprises three complementary determining regions, respective amino acid sequences thereof being positions 46-50, positions 68-73, and positions 112-125 of SEQ ID No. 4. A T cell expressing the TCR can effectively recognize a MART-1 (27-35) epitope polypeptide supported on a T2 cell and secrete IFN-γ, thereby demonstrating the functionality of the receptor. Use of the TCR with a relevant drug target allows for effective drug development.

Provided is a MART-1 (27-35) epitope-specific T cell receptor, comprising an α chain and a β chain. The α chain comprises three complementary determining regions, respective sequences thereof being positions 61-66, positions 84-89, and positions 124-136 of SEQ ID No. 3. The β chain comprises three complementary determining regions, respective amino acid sequences thereof being positions 46-50, positions 68-73, and positions 112-125 of SEQ ID No. 4. A T cell expressing the TCR can effectively recognize a MART-1 (27-35) epitope polypeptide supported on a T2 cell and secrete IFN-γ, thereby demonstrating the functionality of the receptor. Use of the TCR with a relevant drug target allows for effective drug development.

The present disclosure provides drug responsive domains derived from human carbonic anhydrase 2 that can modulate protein stability for human interleukin 15 (EL15) payloads, as well as compositions and methods of use thereof.

The present invention relates to a method for transducing a target cell, the method comprising the step of contacting a target cell with a retroviral vector and a poloxamer having a molecular weight of 12.8 kDa to about 15 kDa. Further, the invention relates to the use of a poloxamer as defined herein, optionally in combination with a polycationic substance as defined herein, for transducing a target cell with a retroviral vector and a kit comprising a retroviral vector, a poloxamer as defined herein and, optionally, instructions for use.

The present invention relates to a method for transducing a target cell, the method comprising the step of contacting a target cell with a retroviral vector and a poloxamer having a molecular weight of 12.8 kDa to about 15 kDa. Further, the invention relates to the use of a poloxamer as defined herein, optionally in combination with a polycationic substance as defined herein, for transducing a target cell with a retroviral vector and a kit comprising a retroviral vector, a poloxamer as defined herein and, optionally, instructions for use.

Provided herein are BCMA-binding molecules, including anti-BCMA antibodies and antigen-binding fragments thereof such as heavy chain variable (VH) regions and single-chain antibody fragments, and chimeric receptors comprising the anti-BCMA binding molecules such as chimeric antigen receptors (CARs). In some embodiments, the anti-BCMA antibodies or antigen-binding fragments thereof specifically bind to BCMA-1. Among the anti-BCMA antibodies are human antibodies, including those that compete for binding to BCMA with reference antibodies, such as a non-human reference antibody. Also provided are genetically engineered cells expressing the CARs or BCMA-binding molecules and uses thereof such as in adoptive cell therapy.