Reprogramming CAR T-Cells with designed bioPROTACs

bioRxiv (Cold Spring Harbor Laboratory) 2026 Preprint Open access

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Authors: Vivek S. Peche, Sebastian Kenny, Tae Gun Kang, Brian Coventry, Tian Mi, Inna Goreshnik, Mariana Garcia Sanchez, Martin Reid, Macey Smith, Dionne K. Vafeados, Rahul S. Kathayat, Yu Kaiwen
+12 more Zuo-Fei Yuan, Long Wu, Anthony A. High, Andrew N. Nemecek, Elizabeth Wickmann, Adeleye Oluwatosin Adeshakin, Francesca Ferrara, Robert E. Throm, Taosheng Chen, Ben Youngblood, David L. Baker, Stephen M Gottschalk
DOI: 10.64898/2026.02.21.706835
Cited by: 1
References: 10

Abstract

Gene editing has been used to enhance CAR T-cell function by disrupting negative regulators but has limitations. Here we show that de novo-designed generated targeted degraders (bioPROTACs) provide an alternative approach. Expression of bioPROTACs in CAR T-cells targeting DNMT3A, a key regulator of T-cell exhaustion, phenocopied gene knockout. Our reversible, non-gene editing approach provides a tunable strategy to reprogram T-cell fate which should be broadly applicable for next-generation cell therapies.

Fields of Study & Subjects

CAR-T cell therapy research Protein Degradation and Inhibitors CRISPR and Genetic Engineering

Publication details

Journal / source
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Publication date
22 February 2026
Language
EN
Document type
Preprint