Pseudotyping Adenoviral Vectors Construction
Numerous biological characteristics of adenoviruses have made them the vehicle of choice for both in vivo and in vitro applications. Although adenovirus gene delivery vectors are valuable in many fields of gene therapy, their broad tropism means that they can't be directed to a specific target cell. Pseudotyping as a general technique describes the use of an exogenous viral envelope glycoprotein to change the tropism of the virus. As a leading expert in gene therapy market, Creative Biolabs provides various pseudotyped adenoviral vector construction services to satisfy clients' requirements through modifying the plasmid encoding the expression of envelope proteins. This enables us to alter the host range and the tissue tropism of adenoviral viral vectors.
Pseudotyping of Adenoviral Vectors
Viral pseudotyping is a strategy to create vectors with new tropism and trafficking properties. Pseudotyping of envelope fusion proteins is a natural adaptive mechanism of viral evolution that has been reported in certain viruses, including adenoviruses. Capsid proteins and envelope glycoproteins take a part in virus attachment and interaction with cellular receptors, deciding cell tropism. Therefore, manipulation of viral surface proteins may improve the transducing ability of these vectors, expanding or limiting their tropism. Furthermore, pseudotyped vectors demonstrate higher transduction titer and efficacy. Pre-existing immunity and diverse tropism restrain the wide use of recombinant adenovirus in gene therapy. These two features can be addressed by modifying immunogenic epitopes of adenovirus capsid, specifically located at hexon.
Figure 1. Strategies used for genetic hexon modification. (Solanki, 2016)
Pseudotyping of Adenoviral Vectors at Creative Biolabs
For the purposes of gene therapy or vaccine application, scientists might either want to expand or limit the range of cells susceptible to transduction by a therapeutic vector. Many commonly used gene transfer vectors have been pseudotyped for clinical practices. At Creative Biolabs, we'd like to help customers to develop pseudotyping adenoviral vectors in which the endogenous viral envelope proteins can be replaced by envelope proteins from other viruses or some chimeric proteins. Such chimera is composed of viral protein parts necessary for incorporation into the virion, together with sequences able to interact with specific proteins of hosts.
Figure 2. Strategy used for the production of pseudotyped adenoviral vectors. (Von Seggern, 2000)
Recombinant adenoviral vectors show extensive promise as pharmaceutical drugs to treat or prevent a variety of human diseases. However, they hold two main issues of in vivo vector toxicity and specificity. Remarkably, we offer customized viral vector construction services to alter adenoviral vector design and improve delivery capacity, for example, pseudotyping serotype 5 vectors with coat proteins originated from alternative serotypes. The resulting pseudotyped adenoviral vector, that is not prone to neutralization and has high target specificity, theoretically allows for a lower dose in administrated in vivo.
Features
- Higher clinical efficiency
- Specific tropism to target cells
- Transduction into more cell and tissue types
- Increased immune response with lower titer
Adenovirus-based gene delivery vectors can efficiently infect many different host cells, making them appealing tools for clinical gene therapy. As an experienced specialist in the biotechnology field, Creative Biolabs provides one-stop services to construct pseudotyping adenoviral vectors to transduce specialized cells with new tropism, which present antigens very effectively and enhance anti-vector immune responses. For more information, please feel free to contact us.
References
- Solanki, M.; et al. (2016). Adenovirus hexon modifications influence in vitro properties of pseudotyped human adenovirus type 5 vectors. J Gen Virol. 97(1):160-168.
- Von Seggern, D.J.; et al. (2000). Adenovirus vector pseudotyping in fiber-expressing cell lines: improved transduction of Epstein-Barr virus-transformed B cells. J Virol. 74(1): 354-362.
