Genetically engineered virus attacking cancer cells.

Can Genetically Modified Viruses Help Fight Cancer? A New Strategy

Nico Varela in Health & Wellness July 2025 • 4 min read.

"Scientists are exploring how to retarget viruses to selectively attack cancer cells, offering a potential breakthrough in cancer treatment."

The fight against cancer is a relentless pursuit, with researchers constantly seeking new and innovative ways to target and eliminate cancer cells. One promising avenue of exploration involves genetically modified viruses. These aren't just any viruses; they're engineered to specifically target and destroy cancer cells while leaving healthy tissues unharmed.

Recombinant adeno-associated viruses (rAAVs) are at the forefront of this research because of their potential as gene transfer vehicles. Think of them as tiny delivery trucks that can carry therapeutic genes directly into cancer cells. The challenge, however, lies in ensuring that these 'trucks' reach their intended destination and don't go off course, infecting other parts of the body.

Recent studies have focused on modifying the outer shell, or capsid, of rAAVs to include tumor-targeting peptides. These peptides act like guided missiles, helping the virus to recognize and bind specifically to cancer cells. The goal is to create a more precise and effective cancer treatment that minimizes side effects and maximizes the therapeutic impact.

How Do Genetically Modified Viruses Target Tumors?

Genetically engineered virus attacking cancer cells.

The secret lies in modifying the virus's capsid, the protein shell that surrounds and protects its genetic material. Scientists genetically insert specific peptide sequences into the capsid. These peptides are designed to bind to unique markers found on the surface of cancer cells, such as integrins, sialyl Lewis X (sLeX), and tenascin C (TnC).

These markers are often overexpressed in tumor cells compared to healthy cells, making them ideal targets for selective binding. By attaching to these markers, the modified virus can specifically enter cancer cells, delivering its therapeutic payload while sparing healthy tissue.

Integrins: These cell surface receptors play a role in cell adhesion and signaling and are frequently upregulated in cancer.
Sialyl Lewis X (sLeX): This carbohydrate structure is involved in cell-cell interactions and is often found on cancer cells.
Tenascin C (TnC): An extracellular matrix protein associated with tissue remodeling and is highly expressed in the tumor microenvironment.

Researchers at the University of Ulsan College of Medicine, Republic of Korea, successfully produced rAAV5 mutants with tumor-homing peptides. These modified viruses effectively transduced human cancer cells expressing the corresponding receptors, and their transduction was significantly suppressed by corresponding antibodies, confirming the specificity of the targeting mechanism. This precision is crucial to reduce toxicity and improve treatment outcomes.

Future Directions and Optimizations

While the initial results are promising, there's still work to be done. Scientists are continually optimizing rAAV5 mutant viruses to enhance their ability to selectively infect cancer cells. This involves identifying the best protruding loop regions on the capsid to insert tumor-targeting motifs and improving the efficiency of gene transfer once the virus enters the cell. The ultimate goal is to develop rAAV5 vectors as a practical tool for gene-based cancer treatment, offering new hope for patients worldwide.

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This article is based on research published under:

DOI-LINK: 10.3892/ol.2011.376, Alternate LINK

Title: Acquisition Of Selective Antitumoral Effects Of Recombinant Adeno-Associated Virus By Genetically Inserting Tumor-Targeting Peptides Into Capsid Proteins

Subject: Cancer Research

Journal: Oncology Letters

Publisher: Spandidos Publications

Authors: Han Saem Lee, Ji Yun Kim, Won Il Lee, Sung Jin Kim, Min Ji Ko, Sunjoo Jeong, Keerang Park, Han Choe, Heuiran Lee

Published: 2011-08-08

Everything You Need To Know

What are genetically modified viruses and how do they help in cancer treatment?

Genetically modified viruses, specifically recombinant adeno-associated viruses (rAAVs), are engineered to target and destroy cancer cells. This is achieved by altering the virus's capsid, the protein shell, to include tumor-targeting peptides. These peptides bind to specific markers on cancer cells, ensuring the virus selectively infects and destroys them while minimizing harm to healthy tissues. rAAVs are used as gene transfer vehicles, carrying therapeutic genes directly into cancer cells.

Why are recombinant adeno-associated viruses (rAAVs) important in cancer research?

rAAVs, particularly rAAV5 mutants, are significant because of their potential to deliver therapeutic genes directly to cancer cells with precision. By modifying the capsid to include tumor-targeting peptides, these viruses can selectively bind to markers like integrins, sialyl Lewis X (sLeX), and tenascin C (TnC) found on cancer cells. This targeted approach minimizes side effects and maximizes the therapeutic impact, offering a more effective cancer treatment. Specificity is confirmed when corresponding antibodies suppress transduction.

How is the virus's capsid modified to target tumors?

The capsid of a virus is modified by genetically inserting specific peptide sequences. These peptides are designed to recognize and bind to markers overexpressed on cancer cells, such as integrins, sialyl Lewis X (sLeX), and tenascin C (TnC). By attaching to these markers, the modified virus can specifically enter cancer cells and deliver its therapeutic payload. The selection of protruding loop regions on the capsid for inserting tumor-targeting motifs is key for enhancing the virus's ability to selectively infect cancer cells.

What is the importance of integrins, sialyl Lewis X (sLeX), and tenascin C (TnC) in this approach?

Integrins, sialyl Lewis X (sLeX), and tenascin C (TnC) are significant because they serve as targets for genetically modified viruses to selectively bind to cancer cells. Integrins play a role in cell adhesion and signaling, sLeX is involved in cell-cell interactions, and TnC is associated with tissue remodeling. All three are frequently overexpressed in tumor cells compared to healthy cells. This overexpression allows the modified viruses to differentiate between healthy and cancerous cells, ensuring targeted delivery of therapeutic genes.

What are the future directions for genetically modified viruses in cancer therapy?

Future optimizations involve enhancing the ability of rAAV5 mutant viruses to selectively infect cancer cells and improving the efficiency of gene transfer once the virus enters the cell. Scientists are focused on identifying the best protruding loop regions on the capsid to insert tumor-targeting motifs. The ultimate goal is to develop rAAV5 vectors as a practical and effective tool for gene-based cancer treatment, offering new and improved options for patients worldwide. Other related concepts not discussed include understanding the immune response to viral vectors and optimizing the therapeutic genes delivered.