Transcription Activator-like Effector Nucleases (TALEN) Based Gene Engineering Service
Transcription activator-like effector nucleases (TALEN) have become an invaluable gene editing tool for researchers for potential gene therapy due to their unique advantage of precise targeting. Our company is committed to providing our customers with an all-in-one solution for gene editing based on TALEN technology, including experimental design, vector construction, and functional validation. Our professional and efficient scientific services can accelerate your rare disease gene therapy development projects.
TALENs are enzymes that target specific DNA sequences and recognize specific DNA base pairs with the help of TAL effectors, proteins secreted by Xanthomonas. TAL effectors can be designed and modified to recognize and bind almost any desired target DNA sequence. Combining TAL effectors with DNA cleavage domains yields restriction endonucleases capable of binding to DNA and cleaving DNA strands at specific sites. This technique has been widely used for gene knockout, knock-in, and transcriptional activation.
Several research groups have reported the application of TALEN technology in gene therapy, such as for the design of stably modified human erythroid cell lines and human induced pluripotent stem cells (hiPSCs). TALEN technology has also been used in vitro to correct genetic errors that cause disease. This technology has also shown potential for use as a tool to control the immune system against cancers. However, uncertainties in TALEN binding specificity and unknown immunogenicity factors have hindered the in situ application of this technology. Recent studies suggest that TALEN technology can be used in combination with other genome engineering tools to fulfill experimental needs.
Fig. 1 Co-delivery of TALENs and donor DNA using helper-dependent adenoviral (HD-Ad) vectors. (Xia E, et al., 2019)
Our advances in precisely targeted regulators of gene expression as well as targeted nucleases allow us to offer our customers TALEN services for gene therapy. Our advanced technology enables the addition and correction of any gene across multiple cell types in humans, offering the possibility of developing gene therapies for rare diseases. Our services include, but are not limited to:
- TALEN design and the prediction of off-targets
We help our customers to find possible TALEN binding sites in specific DNA sequences to correctly design TALEN through various tools such as TALE-NT and TALENoffer. We also provide our customers with unwanted off-target prediction services.
- TALE and TALEN assembly
We help customers construct TALEs and TALEN with tailored DNA-binding specificities through the assembly method of Golden Gate Cloning.
- Optimization of the TALEN architecture
Our researchers have developed obligate heterodimerized TALEN variants to increase target specificity, improve nuclease activity, and reduce toxicity. Moreover, we improved heterodimerized TALEN activity by optimizing the FokI-based TALEN architecture through "Sharkey" mutations. In addition to FokI endonuclease-based TALE nucleases, we also help our customers develop other variants, such as fusing TALE DNA-binding domains to the restriction endonuclease PvuII to obtain TALE-PvuII nucleases.
- TALEN delivery
TALEN can be used as DNA, RNA, or protein. We offer a variety of methods to help our customers deliver them into living cells, including physical methods (such as microinjection or electroporation), virus-based delivery methods (such as adenoviruses, lentiviruses, and baculoviruses), and chemical methods (such as methods that utilize transfection reagents, PEG, or liposomes). We select the appropriate delivery method based on the target provided by our customers. Moreover, for vector-based delivery methods, we provide customers with services to determine the effectiveness of site-specific gene integration.
- Detection of TALEN expression
TALEN is a foreign protein and its prolonged expression in humans may lead to unwanted antigenic reactions. We provide our customers with a time-course analysis of TALEN expression in transduced cells to ensure the safety of in vivo gene therapies.
With a best-in-class technology platform and a dedicated scientific team, our company provides TALEN-based gene-editing services to customers around the world. TALEN effector proteins designed by our researchers have helped our customers advance numerous biomedical applications, including gene therapy for rare diseases. If you need help with TALEN design, please contact us for technical support and solutions.
- Xia, E.; et al. TALEN-mediated gene targeting for cystic fibrosis-gene therapy. Genes, 2019, 10(1): 39.
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