Hepatocellular Carcinoma-targeting Adenovirus Vector Construction Service
Optimizing targeting strategies for vectors in order to enhance anti-tumor activity and secure patient safety is important for cancer gene therapy. At Creative Biolabs, with combined expertise and advanced technologies, we are able to help develop genetically engineered regulated adenovirus that can selectively illuminate and kill cancer cells. Here, we introduce our hepatocellular carcinoma-targeting adenovirus vector construction services to our global clients.
Introduction of Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the fifth most common cancer, causing one-third of cancer-related deaths worldwide. It mostly develops in the cirrhotic liver, which results from different factors, including chronic viral hepatitis, alcohol abuse, inherited metabolic maladies, etc. HCCs are often diagnosed at an advanced stage and therefore, patients have a poor prognosis. Traditional therapeutic approaches, including surgery, chemotherapy, and radiotherapy, have limited efficacy in advanced liver cancer. Thus, novel and effective treatment modalities are urgently needed to improve the situation. Gene therapy, which involves the transfer of a therapeutic gene to diseased cells or tissues using a vector (viral or non-viral), represents a novel promising therapeutic method.
Figure 1. A replication-competent virus is engineered to specifically infect tumor cells, sparing healthy cells. (Kaufmann, 2012)
Adenovirus Gene Therapy for HCC
Adenovirus has been the most common gene transfer vector for cancer gene therapy in the past decades due to a number of unique advantages that make them attractive in gene therapy, including (i) the ability to infect a broad range of cell types with high efficiency and achieve high levels of transgene expression, (ii) capability of transducing both replicating and non-replicating cells, (iii) easy acquisition of high titers, and (iv) stable genome where foreign genes can be inserted and maintained without change through successive rounds of viral replication.
Figure 2. An example of Ad vector engineering strategy for targeting tumor cells. (Wang, 2016)
Because traditional adenovirus lacks the ability to target liver cancer, various strategies have been developed to achieve tumor-specific targeting. Firstly, one strategy is to use cancer or tissue-specific promoter to control the expression of the viral essential gene for replication, which is called the transcriptionally targeted strategy. In this way, the virus could only replicate in tumor cells and kill them. Secondly, the tumor signaling pathway can be targeted by deletion or mutation of key adenovirus genes or some bases that are necessary for adenovirus replication in normal cells but not in tumor cells, such as the E1B 55 kDa gene. Thirdly, as adenovirus efficiently infect host cells by binding to specific receptors via fibers on the capsid, modification of the adenovirus capsid may improve the ability of adenovirus to bind target cells. For instance, antibody-modified or peptide-incorporated adenoviral vectors can be constructed to achieve retargeting.
Features of Our Services
- Customized design and construction of Ad vectors for HCC-targeting purposes
- A full set of in vitro and in vivo assays for testing the accessibility and the potency of regulated Ad vectors
- Safety and toxicology analysis of HCC-targeted Ad vectors
- Optimized technology to simplify and accelerate the construction of Ad vectors within a matter of weeks
At Creative Biolabs, you will find the most comprehensive customized viral and non-viral vector design and construction services at the most competitive prices. We are happy to share our expertise and technologies to promote your project a success. Please contact us for further information about our services and get a quote.
References
- Kaufmann, J.K.; Nettelbeck, D.M. (2012). Virus chimeras for gene therapy, vaccination, and oncolysis: adenoviruses and beyond. Trends in molecular medicine. 18(7): 365-376.
- Wang, Z.; et al. (2016). A novel capsid-modified oncolytic recombinant adenovirus type 5 for tumor-targeting gene therapy by intravenous route. Oncotarget. 7(30): 47287.
