Development of Adaptor-based Viral Vector Systems
The development of transfer vectors that transduce target cells while avoiding effects on non-target cells is critical to the success of gene therapy development. Our company is committed to helping customers build adaptor-based viral vector systems, which are selective and flexible targeting systems that restrict gene transfer to the cell type of interest. Our engineering services for targeted viral vectors will contribute to improving the safety and efficacy of gene therapy for rare diseases.
Background
Selective delivery of genes to the cell type of interest using targeted viral vectors is an effective and safe strategy for gene therapy applications. Pseudotyping of viral vectors is a widely used and promising approach. However, this strategy is hampered by the limitation of the number of viral attachment proteins and the laborious viral engineering required for each new target. To overcome this limitation, it is important to use structural knowledge to guide the modification of viral attachment proteins. The use of adaptor proteins has been explored as an alternative approach.
Adaptors are molecules with dual specificity, characterized by binding a viral attachment protein at one end and a receptor on the target cell at the other. The fact that different adaptors can be easily coupled to the same vector without the need to alter vector structures that may be detrimental to vector production or gene transfer allows for great flexibility and safety in vector targeting strategies using adaptors. Most adaptors have great potential in gene therapy for rare diseases by ablating the native tropism of viral vectors and conferring a new tropism to the desired target to enable targeted gene delivery.
Fig. 1 Fusion of a biotin-specific scFv, which binds only tagged adaptor molecules, to H protein to generate flexible targeted lentiviral vectors. (Cordes N, et al., 2022)
Our Adaptor-based Viral Vector System Development Services
- Development of receptor-ligand complexes as adaptors
- Development of adaptor-based viral vector systems by chemical conjugation
- We offer PEGylation strategies to help customers develop targeted AAV and adenoviral vectors.
- We offer thiol-group coupling systems, which combine the flexibility of adaptor systems with the advantage of stable covalent bonds provided by genetic targeting to introduce full-length proteins and receptor ligands that cannot be introduced by genetic methods, such as fatty acids and small molecules, into non-enveloped vectors.
- Development of adaptor systems using avidin and biotin
- Development of monoclonal antibodies as adaptors
Receptor-ligand complexes are widely used as an important class of adaptors for retargeting vectors. We help customers to genetically fuse viral receptors to the ligands of receptors expressed on target cells to achieve vector targeting. For example, targeting adenoviral vectors to dendritic cells by fusing the ectodomain of the adenovirus receptor to CD40L, a ligand for the CD40 receptor on dendritic cells.
Chemical coupling is a method of coupling adaptors to vectors that involves covalent attachment of the targeting ligand to the vector.
We exploit the high-affinity binding between avidin and biotin to develop adaptor strategies for use with a wide range of viral vectors. The avidin-biotin system is suitable for vector types that can be chemically biotinylated, or that allow the incorporation of a biotin-acceptor peptide (BAP). We have established protocols for the biotinylation of adenoviral vectors, AAV vectors, and vaccinia viral vectors for vector targeting.
We help our customers develop monoclonal antibodies to be used as targeting tools for gene transfer vectors. For example, we insert a region of the bacterial immunoglobulin (Ig) binding protein into the viral attachment proteins of multiple vector systems to specifically bridge to target receptors via antibody specificity. This strategy is more suitable for ex vivo gene therapy applications.
Our company has extensive experience and advanced technology in the development of viral vectors for gene therapy. Our development services for adaptor-based vector systems for targeted gene therapy provide you with the added flexibility to find the option that better suits your rare disease gene therapy development program. If you are interested in our services, please feel free to contact us for more details.
Reference
- Cordes, N.; et al. Adapter-mediated transduction with lentiviral vectors: A novel tool for cell-type-specific gene transfer. Viruses, 2022, 14(10): 2157.
For Research Use Only.
