Overexpressing Virus

Due to the recent description of the pandemic caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the world is facing a major public health crisis. This disease (COVID-19) causes panic worldwide because of its severity, rapid spread, affecting the ability of both lungs and the chance of missed diagnosis. With rich experience in the field of gene therapy, Creative Biolabs has actively developed recombinant overexpression virus based on the targets which play important roles in the infection of SARS-CoV-2, so as to assist the treatment of COVID-19.

Introduction of SARS-CoV-2 Infection

SARS-CoV-2 is a positive-stranded enveloped RNA virus of the Coronaviridae family. After entering the host, usually through atomized virus particles or contact with contaminated surfaces, the virus needs to undergo its biological cycle. Studies on SARS-CoV-2 infected patients have shown that the respiratory tract is the main site of the virus infection.

Fig.1 Structure of SARS-CoV-2. (Cascella, 2020)

Two of the participating factors play key roles:

• Spike (S) Glycoprotein of SARS-CoV-2

The SARS-CoV-2 S glycoprotein plays an important role in the combination with host cells during viral infection. According to reports, SARS-CoV-2 can infect human respiratory epithelial cells through interaction with human angiotensin converting enzyme 2 (ACE-2) receptors. S protein is a large type I transmembrane protein, containing two subunits S1 and S2. S1 mainly contains a receptor binding domain (RBD), which is responsible for identifying cell surface receptors. S2 contains the basic element fusion required for the membrane.

• ACE-2

ACE-2 is an 805 amino acid transmembrane protein, an important member of the renin-angiotensin system, and plays a key role in blood pressure regulation. The common expression of ACE-2 on the surface of the gastrointestinal lumen, most commonly in intestinal epithelial cells, maybe the secondary site of SARS-CoV-2 intestinal infection. Studies have shown that SARS-CoV-2 down-regulates ACE-2 through its S protein, causing severe lung damage. This is the main reason why coronaviruses often cause respiratory diseases.

Fig.2 ACE-2 expression throughout the body and schematic of ACE-2 primary domains. (Gheblawi, 2020)

Overexpressing Virus

As mentioned above, the SARS-CoV-2 S protein directly binds to the ACE-2 receptor on the surface of the host cell to promote virus entry and replication. Studies have shown that excessive ACE-2 may competitively combine with SARS-CoV-2, which not only neutralizes the virus, but also rescues the cellular ACE-2 activity, thereby protecting the lungs from injury.

Viral gene overexpression is a process that leads to the subsequent acquisition of a large number of target gene products, which can be used for research or production and the biological function of target gene products. Based on the important role of S protein and its receptor ACE-2 in the pathogenesis of SARS-CoV-2, we developed the recombinant overexpression virus as a tool for the study of SARS-CoV-2 infection, which will contribute to the development of COVID-19 drugs and vaccines.

At present, we have developed the following four kinds of recombinant overexpression viruses based on lentivirus (LV) and adeno-associated virus (AAV):

LV: LVs are versatile tools because they can transform undifferentiated cells. These viruses can make gene expression stable for a long time and integrate into the host genome permanently.

AAV: AAVs are widely used for gene transfer in vivo because of their mild immune function.

If the product you need is not on the list above, please feel free to contact us. We can customize the overexpressing virus according to your needs.

References

1. Cascella, M.; et al. Features, evaluation and treatment coronavirus (COVID-19). StatPearls Publishing. 2020.
2. Gheblawi, M.; et al. Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2. Circulation research. 2020, 126(10): 1456-1474.