Hypoxia-inducible Adenovirus Vector Construction Service

Creative Biolabs is a leading expert in adenovirus vector construction for gene delivery and gene therapy applications. Based on powerful viral vector construction technologies and abundant experience, we offer a broad range of adenovirus vector construction service at a reasonable cost and quick turnaround time.

Introduction of Hypoxia-induced Expression System

Hypoxia (lowered oxygen conditions) is a common feature of ischemic heart disease and is associated with resistance to anticancer radio- and chemotherapy. More importantly, tumor hypoxia appears to accelerate malignant progression and increase metastasis. Hypoxia is regulated by the hypoxia-inducible factor (HIF), which activates gene expression by binding to the hypoxic-response elements (HREs) within the promoter regions of genes, which regulate biological processes. HIF is a transcription factor that regulates gene expression in response to hypoxia. As a heterodimeric complex, it is composed of an oxygen-sensitive α subunit and a constitutively expressed β subunit. Expression systems with HREs, which are activated by HIF1α, can be exploited for the development of cancer therapeutics targeting tumor hypoxia. In fact, a number of expression systems with HREs have been designed for tumor- or disease-specific gene expression.

Construction of Hypoxia-inducible Adenoviral Vectors

Adenovirus

The hypoxia-induced system has been incorporated into adenoviral vectors for brain and tumors and has shown considerable promise as a strategy for treating cerebral ischemia and tumors. In hypoxia-inducible expression systems, HREs is commonly used to construct inducible adenoviral vectors to express therapeutic genes for the treatment of diseases. Several studies have used HREs sequences in combination with minimal promoters for adenoviral vectors to limit gene expression in hypoxic tumor environments. In addition, adenoviral vectors selectively mediate hypoxia-inducible gene expression in neurons. For example, a combination of neuron restrictive silencer elements (NRSEs), HREs and CMV minimal promoter (CMVmp) is packaged into replication-defective adenovirus to target gene expression selectively in neurons in a hypoxia-regulated manner. The use of HREs to drive transgene expression in adenoviral vectors has the following advantages:

  • The HREs can act as an enhancer to enhance the transcriptional activity of the promoter.
  • The HREs can achieve increased tumor selectivity by targeting the hypoxic environment encountered in tumors.
  • The incorporation of HREs and hypoxia targeting could broaden the therapeutic efficacy of adenovirus.

Application

Studies have demonstrated the potential of hypoxia-inducible adenoviral vectors in tumor-selective gene therapy. Solid tumors, characterized by the presence of hypoxic regions, constitute approximately 90% of cancers and are suitable targets for hypoxia-inducible gene therapy. Furthermore, these hypoxia-inducible adenoviral vectors can be a good complement to current cancer treatments. For example, hypoxia-inducible gene expression can be applied to gene radiation therapy using a radiation responsive element with HREs sequence as hypoxia- and radiation-inducible promoter to reduce the tumor tissue resistance to radiation therapies and chemotherapeutic drugs. Application of hypoxia-inducible adenoviral vectors is not limited to cancer treatment, and it is often used to treat other ischemic diseases in which hypoxia is a common feature, such as ischemic heart disease and ischemic stroke.

Service

As the world's leading provider of viral vectors development service, Creative Biolabs has established a variety of adenoviral vectors construction platforms and technology. Based on this, we provide hypoxia-inducible adenoviral vector construction services to enhance the gene therapy effect of adenovirus. Moreover, other regulated adenoviral vector construction services are also available at Creative Biolabs, including:

For more information, please feel free to contact us.

For research use only. Not intended for any clinical use.