Figure 1. Structure of adenovirus (Viral zone website)
Adenovirus (AdV) is a non-enveloped, double-stranded DNA virus with a diameter of approximately 70-90 nm (Figure 1). Its genome is about 36 kb in size and is divided into early (E1A, E1B, E2, E3, E4), intermediate (IVa2, pIX), and late (L1-L5) transcription units (Figure 2). There are over 50 serotypes of AdV, with Ad5 being the most commonly used. AdVs exhibit tissue tropism and the ability to infect both dividing and non-dividing cells. Commonly used AdV vectors are categorized into conditionally replicating adenoviruses (CRAs; oAds) and replication-deficient adenoviruses. These vectors are widely used in the development of preventive vaccines, therapeutic vaccines, and oncolytic viruses.
Figure 2. Genome structure of adenovirus (A Handbook of Gene and Cell Therapy)
Conditionally replicating AdV vectors can specifically replicate in cancer cells by mutating or altering the expression of the E1 gene. AdV E1A CR2 or E1B55K interfere with the host cell cycle through the retinoblastoma protein (Rb) and p53 signaling pathways, forcing normal cells into the S phase for replication. When E1A CR2 or E1B55K is deleted, cell division is inhibited, preventing viral replication in normal cells but allowing for extensive replication in cancer cells with abnormal Rb and p53 regulation.
Oncolytic adenoviruses (oAds) are engineered viruses based on AdV that can specifically kill tumor cells. They are widely studied and applied due to their broad host range, safety, ease of production, and capacity to carry large exogenous genes.
AdVs are commonly used as oncolytic viruses, and some of the common modification sites include E1A-CR2, E1B-55K, E1B-19K, etc. Additionally, by driving E1A expression with tumor-specific promoters, the targeting of the virus can be enhanced. Alternatively, AdVs can be used as vectors to deliver exogenous immune-related genes, such as IL-12, IFN-γ, GM-CSF, etc. Combined with traditional therapies such as radiotherapy/chemotherapy, or with biological therapies such as monoclonal antibodies or CAR-T cells, these approaches can synergistically kill tumor cells through multiple pathways.
Genevoyager possesses a well-characterized human serum Ad5 strain and a replication-deficient AdV packaging system, enabling the following modifications: 1. Modification of the AdV structural genes; 2. Insertion of tumor-specific promoters into the E1 gene; 3. Modification of E1A-CR2, E1B-55K, E1B-19K; 4. Carrying therapeutic genes, etc. To further enhance its tumor targeting and safety, oncolytic AdVs can also be customized according to client needs.
Name |
Strain |
Modification |
Adstiladrin |
AdV5 |
Replication-deficient, insertion of IFNα2b. |
H101 |
AdV5 |
Deletion of E1B-55 KD and E3 gene segments. |
KD01 |
AdV5 |
Deletion of E1A-CR2, specific promoter-regulated E1A. |
E10A |
AdV5 |
Insertion of Endostain. |
OBP301 |
AdV5 |
E1 modified to hTERT-p-E1A-IRES-E1B. |
Figure 4. A549 cells infected with replicating Ad5 viral particles (Ad5-GFP)
produced by Genevoyager after 120 hours
Figure 5. Replication-deficient AD5 (AD5-GFP-ΔE1/E3, P1 generation, 72 hours)
produced using Genevoyager HEK293 cells