Microfibers help virus fool the body's immune system

July 31, 2012
Bio-macromolecule fibers formed by the electrostatic interaction between plasmid DNA and positively charged peptides.

A key challenge in virus-based gene therapy is avoiding detection by the human immune system so that the virus would not be deactivated before it reaches its intended target. Now, researchers at the Institute of Bioengineering and Nanotechnology (IBN) have succeeded in circumventing the body’s own defense mechanism by combining two IBN innovations.

In a recent study published in Advanced Materials, IBN researchers demonstrated that cancer cells could be more effectively eliminated when therapeutic viruses were encased in microfibers or synthetic tissue fibers.

Using a novel method developed at IBN, the researchers were able to encapsulate an insect with fibers produced from peptides and DNA for gene delivery. As the structure of the microfibers closely resembles human tissue fibers, they were able to ‘disguise’ the virus by reducing the body’s ability to recognize the virus and prevent its premature deactivation. Tests conducted on mice with brain tumor show that the microfiber-coated viruses could significantly slow down tumor growth and prolong survival, in comparison to treatment with uncoated viruses.  

is a technique for correcting defective genes responsible for disease development. It involves using DNA encoded with a functional gene to replace a mutated gene, and viruses that are stripped of its disease-causing ability are used as a tool to deliver the therapeutic gene into the target cells.  

IBN has been investigating the use of engineered insect virus to treat cancer and neurological disorders since 2003, and the first successful gene delivery to human embryonic stem cells using a baculoviral vector was achieved at IBN in 2006. That same year, IBN researchers published a paper in Cancer Research demonstrating the delivery of therapeutic genes by baculoviral vectors for cancer treatment in an animal tumor model.

In trying to prevent the body from disabling the virus before it reaches the diseased cells, the research team led by IBN Group Leader Dr. Shu Wang turned to a unique microfiber fabrication technique developed by Dr. Andrew C. A. Wan at IBN. In the human body, tissue fibers are naturally formed by the assembly of two different types of macromolecules, such as proteins and DNA. Currently, synthetic tissue fibers are fabricated with only one type of biomolecular material because fibers composed of more than one type of biomolecule are difficult to produce.

Using a water-based chemical process, IBN scientists were able to construct tissue fibers from two biomolecular materials – peptides and DNA. The researchers flanked two droplets of the oppositely charged peptide and DNA molecules after it has been dissolved in water. Upon contact, the droplets zipped together to form a two-component fiber. Fiber formation presumably occurs from the electrostatic interaction between the positively charged peptide molecule and the negatively charged DNA molecule. Through the same procedure, baculoviral vectors were added to the DNA solution to coat the virus with the fibers.

Dr. Shu Wang shared, “For the very first time, we have shown that two biomolecules, namely peptides and DNA, can interact with each other to form structured fibers in a test tube. Since these biomolecules are readily metabolized in the human body to naturally occurring molecules and have no adverse toxicity, they hold strong biomedical potential for the delivery of therapeutic drugs, genes, proteins and viruses to combat cancer.”

“This innovative application of microfibers with viral vectors is an exciting development for gene therapy that was made possible through multidisciplinary collaboration between biologists, chemists and materials scientists at IBN. Our fibrous materials are also of great interest as biocompatible tissue engineering scaffolds for applications in regenerative medicine,” said Professor Jackie Y. Ying, IBN Executive Director.

Explore further: Insect virus holds the key to safer stem cell therapy

More information: 1.    J. Yang, et al. “Microfibers Fabricated by Non-Covalent Assembly of Peptide and DNA for Viral Vector Encapsulation and Cancer Therapy,” Advanced Materials, (2012) DOI: 10.1002/adma.201201145.
 
2. J. Zeng, J. Du, N. Palanisamy and S. Wang, “Baculoviral Vector-Mediated Transient and Stable Transgene Expression in Human Embryonic Stem Cells,” Stem Cells, 25 (2007) 1055-1061.
 
3. C. Y. Wang, et al., “Recombinant Baculovirus Containing the Diphtheria Toxin A Gene for Malignant Glioma Therapy,” Cancer Research, 66 (2006) 5798-5806.

4. A. C. A. Wan, et al., “Silica-Incorporated Polyelectrolyte-Complex Fibers as Tissue Engineering Scaffolds,” Advanced Materials, 18 (2006) 641-644.

Related Stories

Insect virus holds the key to safer stem cell therapy

July 29, 2011
The future of regenerative medicine lies in harnessing the potential of the human body to renew and repair itself. Now, scientists at the Institute of Bioengineering and Nanotechnology (IBN), the world’s first bioengineering ...

A promising discovery for breast cancer therapy

April 20, 2012
(Medical Xpress) -- Could engineered human stem cells hold the key to cancer survival? Scientists at the Institute of Bioengineering and Nanotechnology (IBN), the world's first bioengineering and nanotechnology research ...

Recommended for you

Scientists find key to regenerating blood vessels

November 23, 2017
A new study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) identifies a signaling pathway that is essential for angiogenesis, the growth of new blood vessels from pre-existing vessels. The ...

Researchers find infectious prions in Creutzfeldt-Jakob disease patient skin

November 22, 2017
Creutzfeldt-Jakob disease (CJD)—the human equivalent of mad cow disease—is caused by rogue, misfolded protein aggregates termed prions, which are infectious and cause fatal damages in the patient's brain. CJD patients ...

Surprising roles for muscle in tissue regeneration, study finds

November 22, 2017
A team of researchers at Whitehead has illuminated an important role for different subtypes of muscle cells in orchestrating the process of tissue regeneration. In a paper published in the November 22 issue of Nature, they ...

Study reveals new mechanisms of cell death in neurodegenerative disorders

November 22, 2017
Researchers at King's College London have discovered new mechanisms of cell death, which may be involved in debilitating neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.

How rogue immune cells cross the blood-brain barrier to cause multiple sclerosis

November 21, 2017
Drug designers working on therapeutics against multiple sclerosis should focus on blocking two distinct ways rogue immune cells attack healthy neurons, according to a new study in the journal Cell Reports.

New simple test could help cystic fibrosis patients find best treatment

November 21, 2017
Several cutting-edge treatments have become available in recent years to correct the debilitating chronic lung congestion associated with cystic fibrosis. While the new drugs are life-changing for some patients, they do not ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Orwellwasright
not rated yet Jul 31, 2012
The materials described in this article seem suspiciously similar to Morgellons. We all know the government has a history of unauthorized public testing, maybe this helps explain the origin of Morgellons, with the results of the tests being "released" under guise of IBN studies.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.