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Viruses to cure cancers

gene therapy and genome editing are two of the latest advances in treating head and neck cancers, offering new hope for patients and providing exciting new avenues for research and development. (Photo: Canva))

Tue. 21 February 2023

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Gene therapy and genome editing are two of the latest advances in treating head and neck cancers, offering new hope for patients and providing exciting new avenues for research and development.

Can A Secret Viral Vector Cut Through Human Genes To Cure A Deadly Head And Neck Cancer?

Figure 1 Gene therapy technique

Well, the secret viral vector exists! No, it is not a 2022 American teen horror drama film or sci-fi, but a miracle of modern science!

Let us dive deep!

Unfolding the secret viral vector

Viral vectors are vehicles to deliver a gene of interest inside a normal or abnormal cell. This technique is a crucial step in gene therapy.

Gene Therapy is a molecular technique to replace a person’s faulty genetic material with normal genetic material to treat or cure a disease or abnormal medical condition. [4]

It involves the transfer of new genetic material and the manipulation of existing genetic material.

Are the viral vectors real viruses?

Yes, they are real viruses and with a twist! They are modified viruses that introduce specific DNA sequences, regulatory RNAs [1], or other therapeutic substrates into cells. They are primarily drug-delivery vehicles.

They infect both dividing cells and nondividing cells.

Figure 2 Viral vectors entering a cell

Why are viruses the delivery vehicle of choice?

Viruses serve as powerful delivery vehicles [2] because of their ability to enter cells efficiently. They are also adept at gaining access to hard-to-reach and particular cells. Thus, viral-vector gene therapies can potentially modify genes to treat a broad spectrum of diseases.

What are the commonly used viral vectors in gene therapy?

Three viral vector types are the key players in the game:

1. Adeno-associated-virus (AAV) vectors

2. Adenovirus vectors, or

3. Lentivirus vectors

AAV and adenovirus vectors are used for in-vivo gene therapies. Here they are directly administered to patients by infusion or local administration.

Lentivirus vectors are used for ex vivo therapies. In this method, cells harvested from a patient are modified in the lab before retransplantation.

Now that we have unfolded the secrets of viral vectors and how they work let us find out what these miniscule bugs can do to help treat head and neck cancers!

Figure 3 Types of viral vectors

Head and Neck Cancer and Gene Therapy

Head and neck cancer [5] is now the fifth leading cause of cancer incidence. It is also the sixth leading cause of cancer-related death in the world! The goal of cancer gene therapy is to introduce new genetic material into target cells without causing any damage to non-target tissues.

What is gene therapy?

Gene therapy is a medical technique to treat or prevent disease by altering a person’s genetic makeup instead of using drugs or surgery.

Gene therapy is an experimental treatment that uses genes to treat or prevent disease. In the case of head and neck cancer, gene therapy is being studied to target and kill cancer cells while sparing healthy cells.

What are the common gene therapy approaches used in head and neck cancer?

One approach to gene therapy for head and neck cancer involves using viral vectors to deliver therapeutic genes directly to cancer cells. These vectors, such as adenoviruses or lentiviruses, can be engineered to target cancer cells and deliver a gene that causes the cells to die.

Another approach is to use non-viral vectors like liposomes, nanoparticles, or plasmid DNA to deliver therapeutic genes to cancer cells.

Another area of research is the use of oncolytic viruses - modified viruses that selectively infect and kill cancer cells. They could deliver therapeutic genes to cancer cells, activate immune systems, and inhibit cancer growth.

Figure 4 Head and neck cancer

What strategies are used in a gene therapy approach to treat cancer?

The common strategies [3] utilized in a gene therapy approach to cancer include:

  1. Gene addition therapy - addition of a tumor-suppressor gene
  2. Gene excision therapy- deletion of a defective tumor gene
  3. Antisense RNA therapy- down-regulation of the expression of genes that stimulate tumor growth
  4. Suicide gene therapy - activation of prodrugs with a chemotherapeutic effect
  5. Introduction of genes to inhibit tumor angiogenesis.

Advexin or Ad-p53 is the first gene therapy approved for humane use!

It is approved by the China State Food and Drug Administration.

Advexin (INGN 201, Ad5CMV-p53; Introgen Therapeutics, Inc.) is an adenovirus (type 5) viral vector modified by gene therapy [3]

Figure 5 Gene therapy strategies

How does Advexin work?

  1. The p53 gene resides on chromosome 17p in humans
  2. It encodes a 393 amino acid protein and is critical to tumor biology.
  3. Inactivation of the p53 singling pathway can allow the proliferation of damaged cells resulting in a tumor.
  4. The adenovirus is modified by replacing a viral gene component (E1 region) with a normal p53 gene.
  5. This normal p53 gene (Wild type p53 gene) is delivered to a cancer cell through this modified adenoviral vector.
  6. This normal p53 induces the expression of wild-type p53 protein.
  7. It triggers growth arrest or kills the cancer cells (apoptosis) and, thus, inhibits tumor growth.
  8. Several other gene therapy vectors are being tested for their efficacies, e.g., Gencidine and Onyx (DL1520)

Latest advancements in gene therapy to cut through human genes to treat head and neck cancer

Gene therapy and genome editing are two promising approaches for treating head and neck cancers. Gene therapy involves the introduction of new genes or correcting defective genes in cells to treat diseases. On the other hand, genome editing involves precisely modifying specific genes within cells to correct mutations or otherwise modify their function.

One of the most well-known examples is CRISPR-Cas9. This technology allows scientists to easily target and modify specific genes within cells, making it a powerful tool for developing new treatments for various diseases, including head and neck cancer.

In the context of head and neck cancer, researchers are exploring the use of genome editing to repair mutations in cancer-causing genes, restore the function of tumor suppressor genes, or introduce new genes into cancer cells to trigger cell death.

These approaches are still in the early stages of research, but there is hope that they will eventually be able to offer new and effective treatments for head and neck cancer patients.

In conclusion, gene therapy and genome editing are two of the latest advances in treating head and neck cancers, offering new hope for patients and providing exciting new avenues for research and development.

Figure 6 Gene editing (CRISPR_ CAS)

References:

  1. Anderson, Jorge Vazquez, and Lydia M. Contreras. “Regulatory RNAs.” RNA Biology, vol. 10, no. 12, 2013, Pages 1778-1797. Taylor & Francis Online, https://doi.org/10.4161/rna.27102.
  2. Capra, Emily, et al. “Innovation in viral-vector gene therapy: unlocking the promise.” McKinsey, 17 May 2021, https://www.mckinsey.com/industries/life-sciences/our-insights/gene-therapy-innovation-unlocking-the-promise-of-viral-vectors. Accessed 18 February 2023.
  3. Chisholm, E. “Gene therapy in head and neck cancer: a review.” Postgrad Med J., vol. 83, no. 986, 2007, pp. 731–737. National Library of Medicine, 10.1136/pgmj.2007.061994.
  4. Colditz, Graham A. The SAGE Encyclopedia of Cancer and Society. SAGE Publications, Inc., 2015.
  5. “Head and Neck Cancers - NCI.” National Cancer Institute, 25 May 2021, https://www.cancer.gov/types/head-and-neck/head-neck-fact-sheet. Accessed 18 February 2023.

 

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