A hopeful heart
Monday, April 2, 2012
Cardiovascular disease. Coronary artery disease. Congestive heart failure. These heart centralized issues have affected millions of people over the years with limited answers in disease treatment. However, a breakthrough in the area of gene therapy is less than two years from research completion.
The department of chemical engineering within the College of Engineering, Architecture and Technology at Oklahoma State University has been working on vector manipulation, funded by the American Heart Association.
Currently, the use of gene therapy to cure diseases is hindered by its inability to provide a safe and effective delivery to a specific location in the body. A virus provides the ability to target specific cells, but can be dangerous. Because of this, a vector offers the most promise as it serves as a nano-scale transportation device to deliver the gene to the targeted location, while remaining much safer than using a virus.
Dr. Joshua Ramsey, assistant professor of chemical engineering, leads a group of researchers focusing on developing synthetic vectors that are engineered to imitate a virus. By altering viral genes and using synthetic components, this process would trick the body into accepting the vector instead of viewing it as an infectious virus.
“The intent is to develop nanoparticles capable of delivering therapeutic genes to vascular tissue for the treatment of cardiovascular disease,” said Ramsey. “The impact, however, will be much broader. The vector we are working to develop will be modified in the future to target a variety of diseases.”
The long-term goal of this research is to replace the knob and fiber proteins of adenovirus with a synthetic cell-penetrating peptide. This combination of peptide and genetically modified virus would result in a nanoparticle that presents the same efficiency of a virus, but offers flexible targeting and immunity resistance.
The fiberless adenovirus nanoparticle presents significant advantages over the native adenovirus being used. Specifically as it offers flexible targeting to vascular endothelial cells, said Ramsey.
In the past, a patient needing gene therapy treatment had two choices: viral or synthetic vectors. The viral approach presents safety concerns, but is still more effective than synthetic vectors. This research is focused on creating a marriage of these approaches by isolating the functions of the virus and using synthetic materials, such as cell-penetrating peptides, to target and enter diseased cells while avoiding the drawbacks associated with a virus.
Mechanical revascularization is currently common for heart related diseases, but is not always an option for all patients. Thus, this therapeutic approach, through targeted gene delivery, offers hope. There has long been potential in this area, but unfortunately the viral vectors, considered the most efficient and stable approach, has been associated with extreme setbacks including severe immune responses and resistance over time.
Because of this, synthetic vectors have been deemed safer. Yet, the poor efficiency of synthetic vectors has prevented advancement of gene therapy beyond the clinical trial stages. The need for a combination of the effectiveness of viral vectors with the safety of synthetic vectors is what laid the foundation for this research.
By replacing existing knob and fiber proteins with these peptides and targeting ligands, it will allow attachment of the vector to a specific target cell in need of therapeutic treatment. This method, if perfected, would significantly reduce the danger associated with traditional viral gene vectors.
This research is currently at a midpoint for the four-year funded project.
“Most of our studies to date have been proof-of-concept studies intended to verify the usefulness of our overall approach to design a novel vector,” said Ramsey. “The vector will need to be validated in animal trials and eventually transitioned into human clinical trials.”
Ramsey mentions with the long process from lab research to clinical trials, there is significant investment in both time and money. “As long as our approach continues to show promise, however, there is incentive to quickly advance the treatment so patients can benefit from it.”
The impact of this research is expected to enhance the general field of gene delivery by leading to discovery of principles that would enable better design of vectors and increase gene delivery use through effective synthetic nanoparticles.
The College of Engineering, Architecture and Technology at OSU is focused on its core mission of advancing the quality of human life, specifically through instruction, outreach and research.
“There is a growing group of CEAT faculty doing cutting edge research in the biomedical fields and having a real impact on the future of medicine,” said Ramsey. “Gene therapy truly has the potential to change the way we treat disease. Those diseases considered currently incurable could become very manageable.”