In a recent Nature Communications paper published on November 8, 2023, Dr. Zhen Xie’s team from Tsinghua University introduced the PROMITAR platform, designed to enable programmable translational control in circular mRNA, a significant innovation in RNA-based therapeutics.
RNA-based therapeutics, including antisense oligonucleotides, small interfering RNA, and mRNA vaccines, have emerged as promising tools in biomedicine. Among these, circular RNA (circRNA) stands out for its stability and low immunogenicity compared to linear mRNA. Addressing the challenges of manipulating circRNA, this paper introduces the PROMITAR platform, a programmable miRNA-responsive system for controlling IRES-mediated translation in circRNA. This innovative platform facilitates the construction of logic gates and cell-type classifiers, showcasing its potential for identifying specific mammalian cell types and targeted cancer cell treatments.
The PROMITAR platform utilizes hepatitis C virus (HCV) IRES to advance the development of miRNA-responsive IRES translation activators (MITAs). By strategically inserting sequences into key IRES regions, researchers achieved reversible control over protein synthesis in response to specific miRNAs, a process validated in HEK293 and Huh7 cells. The MITAs, crafted with structures like toehold-like, stem-loop, and 3-arm-junctions, enable precise miRNA-specific translation regulation.
Employed further, the platform demonstrates its utility in creating cellular logic gates and classifiers that respond to specific miRNAs, like miR-FF4 and miR-199a, implementing OR, AND, and NOT functions. Moreover, the platform’s adaptation to circRNAs has led to significant strides in cancer therapy, particularly in identifying and eliminating cancer cells through MITAs responsive to miRNAs like miR-21.
PROMITAR’s flexibility is further underscored by extending its principles to the classical swine fever virus (CSFV) IRES, proving its capability for diverse IRES sequence engineering. This adaptability is critical, especially for IRES sequences with less understood structure-activity relationships, where effective distorting sequences can be screened.
The platform’s capacity for integrating both translation activation and repression mechanisms within a single RNA construct marks a novel breakthrough in RNA translational control. This dual functionality, combined with its potential for sophisticated RNA circuit integration and protein-level regulation, positions PROMITAR as a powerful tool in precision medicine, synthetic biology, and targeted cancer therapy. The prospects of this platform in enhancing gene expression control and advancing biomedical applications highlight its potential to revolutionize future therapeutic strategies.
Check out our mRNA service to expedite your vaccine research
Reference:
Ning, H., Liu, G., Li, L. et al. Rational design of microRNA-responsive switch for programmable translational control in mammalian cells. Nat Commun 14, 7193 (2023). https://doi.org/10.1038/s41467-023-43065-w
PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.
Related News
Exploring Tau Protein’s Role in Glaucoma: New Insights and Therapeutic Potential
Glaucoma, a chronic neurodegenerative disorder, leads to irreversible vision loss by damaging retinal ganglion cells (RGCs) and the optic nerve, often associated with increased intraocular pressure (IOP). Despite the benefits of IOP-lowering treatments, the underlying...
FDA-mandated CAR-T monitoring period could be halved, say researchers
In patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL), the two hallmark post-chimeric antigen receptor (CAR)-T therapy toxicities are extremely rare after two weeks, supporting a shorter, more flexible toxicity monitoring period, according to a study...
Ancestral CRISPR-Cas13 Ribonucleases Discovered: Implications for Genome Editing
In a pioneering study published in *Science*, a team of researchers led by Peter H. Yoon and Jennifer A. Doudna from the University of California, Berkeley, has made a remarkable discovery in the realm of CRISPR technology. The team has identified an ancestral clade...
KBI Biopharma Expands Manufacturing Contract with Global Pharmaceutical Company
KBI Biopharma Inc., a JSR Life Sciences company and global cGMP contract development and manufacturing organization (CDMO), has extended and expanded its manufacturing contract with a leading global pharmaceutical company. Originally initiated in 2020, the renewed...
Related Services
