Capsid-modified Adenovirus Vector Construction

The adenovirus had been sequenced entirely and the detailed mechanism of how this virus replicates and assemble is well known. Developing cell-targeting adenoviral vectors has been an effective means of transferring genes in vivo. As a professional supplier in the biological field, Creative Biolabs has new approaches to produce a modified viral genome by genetically manipulating the capsid genes of adenoviral vectors. We provide end-to-end solutions for capsid-modified vector construction services and our valuable toolboxes can overcome some limits of time-consuming and multiple steps for the easy, rapid construction of capsid-modified adenoviral vectors.

Capsid Modifications

Adenovirus structure

Adenovirus is a family of DNA viruses, composed of a double-stranded DNA genome of 36kb encapsulated within the viral capsid. Transduction of the host cell is activated by binding of the coxsackievirus receptor via the knob domain of the fiber protein of the viral capsid. To optimize properties of the adenoviral vector, virus capsid can be modified to retarget vectors or to escape from the immune system. For instance, adenoviral vectors could be altered chemically by units bound to capsid units. Another option to modulate vector features is to utilize other human or non-human adenoviruses for gene transfer. Generally, these serotypes show a lower seroprevalence and assure more efficient transduction of some cell types for defined applications.

Services

Gene transfer via adenovirus-based vectors has widely been used in human gene therapy and clinical trials. The reduction of adenovirus vector-associated innate immune toxicities will greatly broaden the utility of this bio-platform for use in multiple medical applications. At Creative Biolabs, we have developed novel techniques and integrated services to achieve the modification of adenoviral capsids leading to high-level gene expression. And our scientists with years of experience ensure the safety and efficacy of these vectors in targeting a variety of diseases.

Schematic of a typical adenovirus gene transfer vector genome.Figure 2. Schematic of a typical adenovirus gene transfer vector genome. (Campos, 2004)

Knobless Adenovirus Vector Construction Service - The knobless fibers are prototype substrates for versatile addition of targeting ligands to produce truly targeted adenovirus. Our approach to develop targeted adenovirus is to delete the intact fiber knob and replace it with two different protein moieties.

Chimeric Adenovirus Vector Construction Service - The circulating antibodies to adenovirus capsid proteins is a barrier for adenovirus delivery system used in gene therapy. We made efforts to engineer the hexon to evade anti-hexon antibodies by generating chimeric adenoviruses harboring hexons from other serotypes. The constructed vectors rarely cause human infections or use adenoviruses from non-human sources, such as canine, bovine, or ovine.

Peptide-incorporated Adenovirus Vector Construction Service - We provide a popular method of adenovirus targeting by directing the vector towards different cell receptors. Redirecting can be achieved by linking custom-made peptides specifically to cell surface proteins via genetic integration, chemical peptide conjugation or bridging with bifunctional adapter molecules.

Antibody-modified Adenovirus Vector Construction Service - We have developed strategies to alter adenovirus tropism to make feasible cell-specific targeting by using molecular adapter proteins and genetic capsid modifications. The molecular adapters consist of chemically coupled antibody-ligand fusions, diabodies, as well as genetic fusions between ligand or scFvs and the ectodomain of coxsackie adenovirus receptor.

Features

  • A wide range of host with the efficiently infected rate
  • Multiple modification systems can be chosen
  • High-titer stocks of purified virus
  • Transient expression with high-level concentration

Gene therapy is an innovating and appealing strategy for the treatment of many human diseases, which makes use of vehicles for delivering therapeutic genes into the body of patients. The adenovirus with a non-enveloped protein capsid has gained much attention as an efficient vector for gene transfer. As a reliable partner in the gene therapy market, Creative Biolabs provides a diversity of capsid-modified adenovirus vector construction services to satisfy clients' special requirements. For more information, please feel free to contact us.

Reference

  1. Campos, S.K.; et al. (2004). Rapid construction of capsid-modified adenoviral vectors through bacteriophage lambda Red recombination. Hum Gene Ther. 15(11): 1125-1130.
For research use only. Not intended for any clinical use.