Tissue-specific Promoter-regulated Lentiviral Vectors Service
Lentiviral vectors, as efficient gene delivery tools, have achieved significant progress in human gene therapy. Armed with powerful technologies and professional scientists, Creative Biolabs has successfully established an advanced gene therapy platform to provide customized one-stop tissue-specific promoter-regulated lentiviral vectors construction services to global clients.
Lentiviral Vectors with Targeting Specificity
In recent years, lentiviral vectors have been the focus of gene therapy development owing to their outstanding advantages, such as (i) capable to infect both dividing cells and non-dividing cells, even difficult-to-infect cells and terminally differentiated cells; (ii) high efficiency of gene transfection and long-term gene expression; (iii) ability to deliver larger gene fragments and cDNA, etc. Due to these advantages, lentiviral vectors based gene therapy has been widely explored and made great success in the past several years, covering from the treatment of cancers, diabetes, autoimmune disease to vascular transplants.
However, there are still a few aspects to be improved for lentiviruses to serve as ideal viral vectors. Higher targeting specificity and lower toxicity should be firstly considered and optimized. With the progress of genetic engineering technology, there are several ways for lentiviral vectors modification. One important method to increase the specificity of the lentiviral vectors is the introduction of a tissue/cell-specific promoter, which enables lentiviral vectors to specifically express in certain cells types or tissues. Tissue-specific promoter-regulated lentiviral vectors will facilitate the development of gene therapy, especially targeted therapies for cancers and neurological diseases.
Figure 1. Tumorigenic Cell-targeting Lentiviral Vectors. (Ide, 2016)
Tissue-specific Promoter-regulated Lentiviral Vectors Construction
A promoter is a DNA region located upstream towards the 5' end of the gene. The key factors for tissue-specific promoter-regulated lentiviral vectors construction are designation and introduction of a specific promoter since the promoter contains conserved sequences required for RNA polymerase and transcription factors binding. The promoter initiates the mRNA transcription when it is recognized and bound by RNA polymerase. Meanwhile, it contains a binding site for transcription factors, whose responsibility is recruiting the specific RNA polymerase and regulating gene expression in specific cells and time. Therefore, the introduction of different promoters will result in lentiviral vectors with different targeting specificity.
Until now, many kinds of tissue-specific promoters have been discovered and identified, such as albumin promoter in the liver, muscle creatinine kinase promoter in muscle tissue, myelin basic protein promoter in glial cells and oligodendrocytes. Furthermore, several tumor tissue/cell selective promoters also have been isolated, such as α-fetoprotein in the liver tumor, α-lactalbumin and β-lactoglobulin promoters in the breast cancer, L-plastin promoter in the cancer cells, etc.
Figure 2. Improving promoter activity and specificity. (Nettelbeck, 2000)
Services
Creative Biolabs is an expert in terms of gene therapy after years of effort and progress. Our Ph.D. scientists and professional staff are proud to offer targeting modification services to improve the performance of lentiviral vectors for both basic research and clinical applications. Our featured lentiviral vectors services mainly include but not limited to:
- Tissue-specific promoters custom design
- Lentiviral vectors design and preparation
- Construction of promoter-regulated lentiviral vectors
- Detection and verification of optimized lentiviral vectors
- Safety evaluation
If you are working on lentiviral vector-based gene therapy or interested in the optimization of lentiviral vectors, you can directly contact us or communicate with us for more detailed information.
References
- Ide, K.; et al. (2016). An Efficient Construction of Lentiviral Vectors That Identify and Eliminate Tumorigenic Cells in Pluripotent Stem Cells. The American Society of Gene & Cell Therapy. 24: Supplement 1, S94-S95.
- Nettelbeck, D.M.; et al. (2000). Gene therapy: designer promoters for tumor targeting. Trends in Genetics. 16(4): 174-181.