Effective transgene expression is critical for genetically engineered cell therapy. Therefore, one of CAR-T cell therapy's critical areas of interest, both in registered products and next-generation approaches is the expression of transgenes. It turns out that various constitutive promoters used in clinical products may influence CAR-T cell antitumor effectiveness and impact the manufacturing process. Furthermore, next-generation CAR-T starts to install remotely controlled inducible promoters or even autonomous expression systems, opening new ways of priming, boosting, and increasing the safety of CAR-T. In this article, a wide range of constitutive and inducible promoters has been grouped and structured, making it possible to compare their pros and cons as well as clinical usage. Finally, logic gates based on Synthetic Notch have been elaborated, demonstrating the coupling of desired external signals with genetically engineered cellular responses.
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http://dx.doi.org/10.1016/j.omton.2024.200833 | DOI Listing |
Comput Struct Biotechnol J
December 2024
Cell Culture and Fermentation Sciences, BioPharmaceutical Development, AstraZeneca, Cambridge UK.
The secretory capacity of Chinese hamster ovary (CHO) cells remains a fundamental bottleneck in the manufacturing of protein-based therapeutics. Unconventional biological drugs with complex structures and processing requirements are particularly problematic. Although engineered vector DNA elements can achieve rapid and high-level therapeutic protein production, a high metabolic and protein folding burden is imposed on the host cell.
View Article and Find Full Text PDFMol Ther Nucleic Acids
March 2025
Department of Infectious Disease, Imperial College London, London W2 1PG, UK.
Self-amplifying RNA (saRNA) is an extremely promising platform because it can produce more protein for less RNA. We used a sort and sequence approach to identify host cell factors associated with transgene expression from saRNA; the hypothesis was that cells with different expression levels would have different transcriptomes. We tested this in CDK4/hTERT immortalized human muscle cells transfected with Venezuelan equine encephalitis virus (VEEV)-derived saRNA encoding GFP.
View Article and Find Full Text PDFJ Orthop Translat
January 2025
Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Rd, Nanjing, 210029, China.
Background: Intervertebral disc degeneration (IVDD) stands as a primary pathophysiological driver of low back pain, yet no therapeutic intervention effectively arrests its progression. Evidence shows that certain Sirt1 agonists may confer protective effects on intervertebral discs, but the underlying mechanisms remain unclear. This study aims to delineate the interaction between Sirt1 and the inflammatory microenvironment, offering potential novel avenues for IVDD prevention and treatment.
View Article and Find Full Text PDFZool Res
January 2025
Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea. E-mail:
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features, including amyloid-β plaques, neurofibrillary tangles, and reactive astrogliosis. Developing effective diagnostic, preventative, and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease. Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Forestry, Guangxi University, Nanning 530004, China; Guangxi Key Laboratory of Forest Ecology and Conservation, College of Forestry, Guangxi University, Nanning 530004, China. Electronic address:
Gibberellins (GAs) are a group of diterpene plant hormones that regulates various plant developmental processes, including wood formation. Nevertheless, the regulatory pattern and the downstream targets of GA in the regulation of xylem expansion and cell lignification in woody plants remains unclear. In transgenic Jatropha curcas with significantly increased or decreased bioactive GA content via separate overexpression of JcGA20ox1 or JcGA2ox6, comparative transcriptomic, metabolomic and physiological investigations were conducted on the young stems.
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