Oncolytic adenovirus (Ads) is the most commonly used oncolytic virus (OV) in clinical studies, and it is also the first commercialized oncolytic viral drug. By reconstructing the genome of oAds, it can effectively avoid unwanted cell or tissue damage, and ensure effective anti-cancer efficacy and cancer selectivity. With years of experience in OV development, Creative Biolabs commits to providing clients with professional and customized oAds construction strategies.
Ads belong to the family Adenoviridae. Ads are divided into seven subspecies from A to G and more than 110 genotypes. Ads are non-enveloped viruses with an icosahedral structure and contain a 36-38 kb size double-stranded DNA. The genome can be divided into early genes (E1A, E1B, E2B, E2A, E3, E4) and late genes (L1, L2, L3, L4, L5)1. When adenovirus infects and internalizes into target cells, early genes begin to be expressed, regulating the genes that are required for adenoviral protein synthesis and replication, and late genes begin to be expressed after viral replication, and are associated with cell lysis.
Fig.1 The structure and the genome organization of Adenovirus.2
The capsid and the genome constitute the adenovirus structure. Hexon, penton, fiber, pⅢa, pⅧ, and pⅨ constitute the capsid, modification of which can reduce the immunogenicity of Ads.
Different subspecies of Ads dependent on different cellular receptors, the subspecies A, C, E, and F rely on the coxsackievirus and adenovirus receptors (CAR), the subspecies B and D bind to CD46, CD86, CD80, and DSG-2, integrin ανβ3/5 is used as the secondary receptor of all the subspecies of Ads. Ad2 and Ad5, both subspecies C, are commonly used gene therapy tools. Ads can spread through the respiratory tract, causing gastrointestinal and respiratory symptoms and conjunctivitis.
Tab.1 The subspecies, serotypes, receptors, and associated disease of human adenovirus.
Species | Serotypes | Receptors | Disease |
---|---|---|---|
A | 12, 18, 31 | hCAR | Obesity or adipogenesis |
B | 3, 7, 11, 14, 16, 21, 34, 35, 50, 55 | CD46, CD80, CD86, DSG-2 | Respiratory disease, conjunctivitis |
C | 1, 2, 5, 6, 5, 7 | hCAR, HSPG, VCAM-1, SR, MHC-1-α2 | Respiratory disease, obesity, or adipogenesis |
D | 8-10, 13, 15, 17, 19, 20, 22-30, 32, 33, 36-39, 42-54, 56, 58-60, 62-65, 67, 69-75 | hCAR, SA, CD46, GD1a/Sialic acid | Conjunctivitis, obesity or adipogenesis |
E | 4 | hCAR | |
F | 40, 41 | hCAR | Gastroenteritis |
G | 52 | nd | Gastroenteritis |
Through precise modification of the Ads genome, it is possible to achieve the attenuation of adenoviruses and their specific replication within tumor cells. When the early genes E1A, E1B, and E3 of Ads are moderately deleted or engineered (such as deleting the E1A-CR2 region, E1B-19k, E1B-55k, E3-gp19k, etc.), the replication of Ads in normal cells can be effectively suppressed, thereby enhancing safety. By introducing a tumor tissue-specific promoter (TSP) to replace the native Ads promoter, specific replication of Ads within tumor cells can be accomplished. TSPs include those that are expressed in all tumors, such as the survivin promoter, COX-2 promoter, and human telomerase reverse transcriptase (hTERT) promoter, as well as promoters specific to certain tumors, such as prostate-specific antigen (PSA), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA).
Fig.2 Genomic differences between wild type and mutant Ads.3
Fig.3 The methods to enhance the targeting of oAds to tumors.3
Based on our advanced OncoVirapy™ platform, we provide professional oncolytic adenovirus construction and production services.
Fig.4 Workflow for Creative Biolabs construction of oncolytic adenoviruses.
As an emerging force in the field of tumor therapy, oncolytic adenovirus is being explored and studied continuously. By optimizing the construction strategy of oncolytic adenovirus, the potential side effects of oncolytic adenovirus can be effectively reduced and its targeted killing ability to tumor cells can be enhanced. With extensive industry experience, Creative Biolabs provides comprehensive and customized oncolytic adenovirus cloning and construction services. In addition, we provide a one-stop service for oncolytic adenoviruses from in vitro cell experiments to in vivo animal model validation. If you have any questions or needs regarding oncolytic adenovirus construction services, please feel free to contact us and we will be glad to serve you.
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