دورية أكاديمية
Ultrashort‐Peptide‐Responsive Gene Switches for Regulation of Therapeutic Protein Expression in Mammalian Cells
| العنوان: | Ultrashort‐Peptide‐Responsive Gene Switches for Regulation of Therapeutic Protein Expression in Mammalian Cells |
|---|---|
| المؤلفون: | Jinbo Huang, Shuai Xue, Yu‐Qing Xie, Ana Palma Teixeira, Martin Fussenegger |
| المصدر: | Advanced Science, Vol 11, Iss 28, Pp n/a-n/a (2024) |
| بيانات النشر: | Wiley, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Science |
| مصطلحات موضوعية: | diabetes, gene circuits, gene switches, synthetic biology, Science |
| الوصف: | Abstract Despite the array of mammalian transgene switches available for regulating therapeutic protein expression in response to small molecules or physical stimuli, issues remain, including cytotoxicity of chemical inducers and limited biocompatibility of physical cues. This study introduces gene switches driven by short peptides comprising eight or fewer amino acid residues. Utilizing a competence regulator (ComR) and sigma factor X‐inducing peptide (XIP) from Streptococcus vestibularis as the receptor and inducer, respectively, this study develops two strategies for a peptide‐activated transgene control system. The first strategy involves fusing ComR with a transactivation domain and utilizes ComR‐dependent synthetic promoters to drive expression of the gene‐of‐interest, activated by XIP, thereby confirming its membrane penetrability and intracellular functionality. The second strategy features an orthogonal synthetic receptor exposing ComR extracellularly (ComREXTRA), greatly increasing sensitivity with exceptional responsiveness to short peptides. In a proof‐of‐concept study, peptides are administered to type‐1 diabetic mice with microencapsulated engineered human cells expressing ComREXTRA for control of insulin expression, restoring normoglycemia. It is envisioned that this system will encourage the development of short peptide drugs and promote the introduction of non‐toxic, orthogonal, and highly biocompatible personalized biopharmaceuticals for gene‐ and cell‐based therapies. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2198-3844 63886820 |
| Relation: | https://doaj.org/toc/2198-3844 |
| DOI: | 10.1002/advs.202309411 |
| URL الوصول: | https://doaj.org/article/81ea40474b714dc988a9eff638868201 |
| رقم الأكسشن: | edsdoj.81ea40474b714dc988a9eff638868201 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 21983844 63886820 |
|---|---|
| DOI: | 10.1002/advs.202309411 |