Provided herein are targeting constructs for sustained transgene expression of inducible cell death systems that include mutants of estrogen receptor alpha ligand binding domain (ER-LBD). Also provided are methods for use of the same, such as inducing cell death in a cell.

Provided herein are immune cells expressing antigenic receptors, such as a chimeric antigen receptor and a T cell receptor. Further provided herein are methods of treating immune-related disorder by administering the antigen-specific immune cells.

Provided polynucleotide constructs for the adipocyte-specific production of a cytotoxic protein. Also provided are formulations and systems, including lipid-based delivery vectors for the delivery of polynucleotide constructs as well as methods for making and using such nucleic acid-based polynucleotide constructs, formulations, and systems for reducing growth and/or survival of adipocytes. Compositions, systems, and methods disclosed herein can be used for reducing adipocytes or adipose volume in visceral, subcutaneous, and abdominal fat.