Leukemia Virus
Lentiviral vectors (LVs) are potent vectors for gene transfer in mammalian cells because of their ability to maintain long latency and persistent infection in non-dividing and dividing cells. As a retroviral vector, LV can incorporate envelope glycoprotein (Env) from other enveloped viruses in its viral particles, a feature known as pseudotype. The Env glycoprotein affects the structure and stability of the LV vector, interaction with target cells and LV behavior and the tropism of LV during infection.
To overcome the adverse effects of Env glycoprotein on LV, Creative Biolabs's gene therapy team offers state-of-the-art lentiviral glycoprotein modification services to meet the needs of our clients' LV-based research and preclinical applications.
Introduction of Leukemia Virus
Here, we focus on an important class of LV pseudotypes that target cancer cells and astrocytes - Leukemia virus. Leukemia virus is a retrovirus that infects T cells (a white blood cell) and causes leukemia and lymphoma, also known as human T cell leukemia virus type 1 (HTLV-1) or human T cell lymphocyte virus type 1. The HTLV virus family is a group of human retroviruses that are reported to cause adult T cell leukemia (ATL), HTLV-1 associated myelopathy/tropical lower extremity paralysis (HAM/TSP) or some other diseases. However, due to HTLV-1 infection can't be cured or treated, and most (95%) infected people have no obvious symptoms throughout their life, it is considered a lifelong disease.
Figure 1. Human T-cell leukemia virus type I. (From ViralZone)
Services at Creative Biolabs
The leukemia viral Env complex is the primary "prey" for neutralizing antibody-based vaccine development. The functional Env complex of leukemia virus is composed of gp120 and gp41 trimers, and a single subunit has been shown to be unsuccessful as a vaccine, probably because it is not like a functional Env complex. The variable domains and carbohydrates block the susceptible neutralizing epitopes on the functional leukemia virus Env complex. To obtain a pseudotyped lentiviral vector for targeting cancer cells and astrocytes, our gene therapy team has developed the following glycoprotein modification strategies to generate the optimal leukemia virus Env:
- Improvement of immunogenicity of gp120 by deletion of variable loops (V1, V2 and V3 loops)
- Introducing a loop to remove Env variants to allow optimization by forced virus evolution
- Disulfide bond structure change
- Replacement of hydrophobic residues of hydrophilic and charged residues
- Optimization of the distal portion of gp120 and gp41 to increase the sensitivity of neutralizing antibodies
Following glycoprotein optimization of the virus of interest to you, Creative Biolabs performs binding assays of pseudotyped leukemia virus particle complex to ensure the effect of glycosylation of the protein on viral function. Based on structural optimization, we also offer a range of downstream services such as Potency Tests for Gene Therapy Products, Safety and Toxicology Analysis, Delivery Systems Development, etc. to meet your needs.
Please feel free to contact us and our experienced technicians will give you the most detailed answers to your questions.
References
- Bontjer, I.; et al. (2009). Optimization of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins with V1/V2 Deleted, Using Virus Evolution. Journal of Virology. 83(1):368-383.
- Clarke, E.C.; et al. (2017). Production and Purification of Filovirus Glycoproteins in Insect and Mammalian Cell Lines. Scientific Reports. 7(1):15091.
