Genetic Incorporation Services of Targeting Ligands
Our company is committed to providing customers with genetic incorporation of targeting ligands including peptide ligands and small peptide motifs to achieve the desired targeting specificity of viral vectors. However, the insertion of peptides may disrupt the multimerization of capsid monomers and reduce the thermal stability of the assembled viral vector. We therefore also offer our customers high throughput library screening to enhance the utility of this technology. Our aim is to provide our customers with genetically modified vectors with broadened tropism, specific targeting, or ablated native tropism.
To avoid the potential complexity of adaptor-based viral vector systems, researchers have developed genetic modifications to viral vectors involving the genetic incorporation of targeting ligands. Several research groups fuse the targeted ligand into the envelope protein or capsid of the viral vector to generate a single virion molecule that recognizes the target cell. While this strategy is technically challenging compared to adaptor-based approaches, this single-component systems allow for the production of homogenous retargeted viral vector particles. In addition to this, this strategy eliminates the need to design and develop separate adaptor molecules, facilitating the high-titer production of viral vectors in gene therapy of rare diseases.
Fig. 1 Overview of library protein engineering strategies for viral vectors. (Schaffer D V, et al., 2008)
- Genetic incorporation of polypeptide ligands into viral vectors
- We offer single-chain antibody methods for a variety of vectors including adenovirus, AAV, retrovirus, herpes simplex virus, and measles virus. As an example, we inserted a human low-density lipoprotein receptor (LDLR) specific single chain antibody (scFv) into ecotropic envelope proteins to mediate specific retroviral transduction of LDLR-expressing cells.
- We offer genetic incorporation of other complex peptide ligands such as cytokines and growth factors to produce highly specific viral vectors, such as the viral vector expressing the collagen-binding portion of von Willebrand factor (vWF), that can be used to target tumor sites where angiogenesis occur.
- Genetic incorporation of small-peptide motifs into viral vectors
- Library screening services
- We help our customers generate highly diverse viral libraries by displaying random peptides at specified locations, random insertional mutagenesis, random point mutagenesis, and in vitro recombination and obtain the desired gene delivery properties by screening the libraries.
- In addition, we offer services to select vectors with new tropisms from viral libraries through a selection strategy that focuses on specific cell types.
- Ablation of native vector tropism
Small motif peptides can be incorporated into various regions of the protein with little or no effect on the structure of the viral attachment protein and can be used to target viral vectors to a wide range of cell types. We typically use RGD motif-containing small peptides targeting integrin vectors or poly-lysine (pK7) peptides targeting heparan sulphate vectors to facilitate the targeting of tumor cells. In some cases, we use RGD and pK7 in combination to improve the efficiency of vector delivery.
In the case of systemic applications, it is essential to modify or eliminate the natural viral tropism to avoid the transduction of non-target tissues. We help our customers ablate the natural vector tropism of gene therapy vectors through the addition of targeting ligands. We also offer rational point and domain mutagenesis to reduce off-target infections.
Equipped with a dedicated research team and advanced technology, our company is committed to providing customers with genetic incorporation of targeting ligands to produce viral vectors with the desired target specificity. At our company, our scientists specializing in viral vector development will work with you to develop the most appropriate strategy and provide you with the most meaningful data for the development of gene therapies for rare diseases. If you are interested in our services, please feel free to contact us for more details.
- Schaffer, D. V.; et al. Molecular engineering of viral gene delivery vehicles. Annu. Rev. Biomed. Eng., 2008, 10: 169-194.
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