Peptide-incorporated Adenovirus Vector Construction Service
Adenovirus (Ad)-based vectors are broadly used as gene delivery vehicles for human gene therapy due to their ability to transduce a wide range of cell types, the capacity to incorporate a substantial amount of heterologous DNA, and the lack of oncogenicity in humans. However, some of the biological features of Ad vectors limit their utility as gene therapeutic agents, such as the lack of specificity of a vector for diseased tissues and poor infectivity with a number of cell targets.
With solid expertise in viral vector design and construction, Creative Biolabs offers customized capsid-modified Ad vector construction services to optimize the Ad vector system to suit specific applications. Here, we introduce our peptide-incorporated Ad vector construction services to global clients.
Incorporation of Peptides into Ad Capsid for Virus Retargeting
Successful application of Ad vectors as transfer vehicles requires efficient transduction of the respective targets cells without affecting non-target cells. However, the native tropism of the viruses restricts their ability to transduce some tissues of interest, rarely satisfying the therapeutic need. Genetic modification of the capsid is a potential strategy to modify vector tropism to generate novel viral tropism or achieve more specific targeting, thereby overcoming the limited infectivity associated with deficiency of viral receptors. Studies have reported the insertion of heterologous peptide ligands into different sites of the Ad capsid, such as the fiber knob, the hexon, the penton base, and capsid protein IX (pIX). For instance, Uusi-Kerttula et al. (2015) reported the generation of Ad5 vectors with altered tropism for epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor 1 (FGFR1) by incorporating peptides that bind to either EGFR or FGFR1 to the fiber knob domain to circumvent preexisting Ad5 immunity and improve Ad5 efficacy.
Figure 1. Structural proteins associated with the Ad capsid. (Hall, 2013)
Incorporation of Antigenic Peptides into Ad Capsid for Vaccine Approach
Ad vectors have also been used to develop viral-vector vaccine. Traditionally, the vectors use the host-cell machinery to express antigens that are encoded as transgenes within the viral vector. However, one drawback to this transgene expression of antigen is the inability of Ad-based vectors to produce a potent humoral response against certain antigens. Therefore, the incorporation of antigenic peptides within the capsid structure of viral vectors has been developed as a way to improve vaccine schemes. Incorporating immunogenic peptides into the Ad capsid offers potential advantages, such as stronger immune responses.
Features of Our Service
- Customized design and construction of peptide-incorporated Ad vectors for both targeting and vaccine applications
- A full set of in vitro and in vivo assays for testing the accessibility and the potency of the peptide-incorporated Ad vectors
- Safety and toxicology analysis of peptide-incorporated Ad vectors
- Optimized technology to simplify and accelerate the construction of Ad vectors within a matter of weeks
Creative Biolabs is happy to apply our expertise and technologies to help our clients develop vector systems to accelerate gene therapy, immune-oncology, and vaccination development. Please contact us for further information about our services and get a quote.
References
- Hall, K.; et al. (2010). Unity and diversity in the human adenoviruses: exploiting alternative entry pathways for gene therapy. Biochemical Journal. 431(3): 321-336.
- Uusi-Kerttula, H.; et al. (2015). Incorporation of peptides targeting EGFR and FGFR1 into the adenoviral fiber knob domain and their evaluation as targeted cancer therapies. Human gene therapy. 26(5): 320-329.
