Antibody-modified Adenovirus Vector Construction Service
Adenovirus (Ad) vectors are the most commonly used system for gene therapy applications, due in part to their ability to infect a wide range of cell types and tissues. However, to achieve successful gene therapy, the appropriate genes must be delivered to and expressed in target cells, without harming non-target cells. During the past years, many efforts have been made by scientists to develop technologies and strategies to alter the Ad surface, thereby achieving cell-specific targeting. Antibodies and antibody-derived moieties are potentially useful agents that can be attached to the Ad surface to provide target-specific gene transfer due to their unparalleled affinity and specificity of binding to a wide range of target cell surface markers.
At Creative Biolabs, with solid expertise and optimized technology, we are ready to offer unparalleled Ad vector design and construction services to our global clients. Here, we introduce our antibody-modified Ad vector construction services to facilitate retargeting Ad infection specificity.
Strategies for Antibody-modified Ad Vector Construction
The strategies for the construction of antibody-modified Ad vectors are divided into two types: covalent or noncovalent attachment of targeting antibodies to the capsid and genetic modification of capsid proteins. Genetic modification involves the cloning of the targeting antibody fragment directly into the virion coat proteins. For instance, Poulin et al. (2010) reported genetic fusion of a single-chain antibody (scFv) or single-domain antibody (sdAb) to capsid protein IX (pIX). The results showed that sdAb can be displayed on the pIX to achieve enhanced virus infection of cells expressing the targeted receptor. Besides, Kaliberov et al. (2014) genetically incorporated an anti-carcinoembryonic antigen (CEA) sdAb into a de-knobbed Ad5 fiber-fibritin chimera and demonstrated selective targeting to the cognate epitope expressed on the membrane surface of target cells.
Figure 1. Strategies of Ad vector targeting using bispecific antibodies. (Dmitriev, 2016)
On the other hand, covalent and noncovalent methods involve the addition of targeting antibodies after the virus has been purified, through the use of bispecific antibodies (one binding the Ad virion and the other binding the desired cellular ligand) or antibody-receptor ligand complexes. For instance, Korn et al. (2004) generated two recombinant bispecific antibody molecules for the retargeting of adenoviral vectors to CEA-expressing tumor cells. Besides, Glasgow et al. (2009) reported the formation of an scFv-targeted Ad vector via highly specific association of the Ad virion and a targeting scFv employing synthetic leucine zipper-like dimerization domains. The results showed that zipper-tagged virions and scFv provided target-specific gene transfer. Additionally, studies have also reported that an IgG Fc-binding motif can be genetically incorporated into the capsid to bind monoclonal antibody for selective gene delivery.
Features of Our Services
- Customized design and construction of antibody-modified Ad vectors for different targeting purposes
- A full set of in vitro and in vivo assays for testing the accessibility and the potency of the antibody-incorporated Ad vectors
- Safety and toxicology analysis of antibody-incorporated Ad vectors
- Optimized technology to simplify and accelerate the construction of Ad vectors within a matter of weeks
If you are interested in the antibody-incorporated Ad vector construction services at Creative Biolabs, please contact us to discuss your specific requirements. We are willing to share our expertise with our clients to facilitate their brilliant studies.
References
- Poulin, K.L.; et al. (2010). Retargeting of adenovirus vectors through genetic fusion of a single-chain or single-domain antibody to capsid protein IX. Journal of virology. 84(19): 10074-10086.
- Kaliberov, S.A.; et al. (2014). Adenoviral targeting using genetically incorporated camelid single variable domains. Laboratory investigation. 94(8): 893.
- Korn, T.; et al. (2004). Recombinant bispecific antibodies for the targeting of adenoviruses to CEA‐expressing tumor cells: a comparative analysis of bacterially expressed single‐chain diabody and tandem scFv. The Journal of Gene Medicine: A cross‐disciplinary journal for research on the science of gene transfer and its clinical applications. 6(6): 642-651.
- Glasgow, J.N.; et al. (2009). A strategy for adenovirus vector targeting with a secreted single-chain antibody. PloS one. 4(12): e8355.
- Dmitriev, I.P.; Kaliberov, S.A. (2016). Targeted Adenoviral Vectors I: Transductional Targeting. Adenoviral Vectors for Gene Therapy. Academic Press. 231-257.
