miRNA-Regulated Lentiviral Vectors Service
miRNA-regulated lentiviral vector is a combination of specifically expressed miRNAs with lentiviral vectors as an optimized gene delivery system to achieve a better therapeutic effect. Equipped with powerful genetic technologies and experienced expert team, Creative Biolabs provides comprehensive custom lentiviral vector services based on the value of high-quality and time-saving.
miRNA Based Gene Therapy
microRNA (miRNA) is a class of non-coding single-stranded RNAs with 21-24 nucleotides encoded by endogenous genes. Over a thousand of miRNAs have been identified since the first discovery in 1993. These miRNAs have been indicated to play critical functions in a series of important biological processes (such as cell cycle, differentiation, apoptosis, stress response) through the regulation of gene expression. The dysregulation of miRNA in different tissues or stages will result in a variety of pathological conditions, including cancers, metabolic disorders, neurological diseases, etc. Besides, both biofunctions and diversity of miRNAs lay the foundation of the favorable application of miRNAs in the gene therapy.
miRNAs based gene therapy is mainly embodied in the application for cancer gene therapy, which is owed to its significant reverse regulation of target genes. The expression inhibition or target recognition dysregulation of miRNA is the original cause of abnormal levels of tumor-associated proteins, further leading to abnormal proliferation, differentiation or apoptosis of tumor cells. Therefore, the main principle of miRNAs-based gene therapy is accurate miRNA delivery to tumor sites by a vector system functioning as a negative regulator of tumor-associated genes expression.
Figure 1. Principle of microRNA-mediated suppression of transgene expression and viral replication. (Geisler, 2016)
miRNA-Regulated Lentiviral Vectors
Lentiviral vector is a class of delivery system using lentiviruses as vectors to transfer a gene of interest into the cells in vivo, which plays an irreplaceable role in gene therapy. But generally constructed lentiviral vectors are capable to infect a wide range of cell types with no selectivity and specificity. Definitely, the miRNA-regulated lentiviral vector is a type of modified ideal gene delivery system with several advantages:
- The tissue, activation or differentiation-specific expression pattern of miRNAs enhance the specificity and safety of the lentiviral vectors.
- Lentiviral vector can protect miRNAs from degradation by circulation or nucleases in the cytoplasm, by which miRNA not only regulates the specificity of the lentiviral vector but also functions to regulate the gene expression of targeted tissues.
An excellent example for miRNA-regulated lentiviral vectors in gene therapy is the application in hemophilia B treatment in mice using a microRNA-regulated lentiviral vector by Brown et al. Compared with common lentiviral vectors, optimized lentiviral vectors containing hematopoietic-specific microRNA (miR-142-3p) could sustainably transfer genes in hemophilia B mice with good target specificity. The activity of factor IX in miR-142-3p-regulated lentiviral vectors treated mice was higher than those untreated group. More importantly, no anti-factor IX antibody and immune response were detected.
Figure 2. Schematic of the miR-ON system using lentiviral vectors in the indicated conditions. (Geisler, 2016)
Services
As an experienced expert in the field of gene therapy, Creative Biolabs has made remarkable achievements in viral vector construction during the past decade. We provide a series of lentiviral vectors services for gene therapy, covering from the design and construction of the lentiviral vectors, safety determination to lentiviral vectors titration, as well as other tailored services.
What you need to do is just contact us or communicate with us for more detailed information.
References
- Geisler, A.; Fechner, H. (2016). MicroRNA-regulated viral vectors for gene therapy. World Journal of Experimental Medicine. 6(2): 37-54.
- Brown, B.D.; et al. (2007). A microRNA-regulated lentiviral vector mediates stable correction of hemophilia B mice. Blood. 110(13): 4144-4452.
