Interdisciplinary Initiatives Program Round 11 - 2022
Xiaojing Gao, Chemical Engineering
Possu Huang, Bioengineering
Ash Alizadeh, Medicine (Oncology)
To increase the precision/efficacy of gene therapy and cell therapy, one promising approach is to use engineered intracellular proteins, such as transcription factors, to control cells. However, most such proteins engineered to date are easily detectable by our immune system, which would either interfere with the function of the proteinexpressing cells or trigger adverse immune responses. Combining our experimental platform and two computational pipelines, here we aim to demonstrate the possibility of dual-objective engineering: creating transcription factors that meet the requirements of both targeting programmable sites and being “invisible” to the immune system. The transcription factors will be immediately useful as control knobs in gene and cell therapies, and the workflow established here will be generalizable to other key proteins in biomedical engineering. The Gao lab are experts in the engineering and testing of biomolecules in mammalian cells. The Huang lab are experts in the computational design of functional proteins, and especially protein-nucleic acid interaction for the purpose of this proposal. The Alizadeh lab are experts in the computational prediction and experimental prediction of peptide immunogenicity. For this project, we will combine our respective expertise, and we expect to demonstrate a proof of principle of human-compatible biomolecular engineering.