Ground-breaking process for gene therapy
Researchers led by Dr Wenxin Wang of UCD Charles Institute & School of Medicine & Medical Science have developed a ground-breaking synthesis process for polymers that will allow new compounds for gene therapy applications to be easily made. The details of their new polymerisation strategy are published today in the scientific journal, Angewandte Chemie.
Polymers are a broad class of natural and synthetic compounds, built up of many smaller parts or monomers that connect together in fast growing chains. Until now, creating more complex branched polymers has been challenging, labour intensive and time consuming.
The Wang group first developed a simple ‘one-pot’ procedure named ‘vinyl oligomer combination’ that lends itself to easy up-scale of the synthesis process. Using kinetic control and statistical manipulation, this new technique is superior in making hyper-branching polymers that spread outwards with the functional component at the ends like a tree and its leaves.
By inserting a cationic component, the team managed to make a series of positively-charged (cationic) polymer trees consisting purely of short branches. With their tree-like structure, these polymers are an effective vehicle for gene delivery to cells; holding therapeutic DNA tightly at the ends, condensing it and navigating through different extracellular and intracellular barriers before delivering this cargo to its final destination in the cell nucleus.
"The degree of branching was found to have a big impact on the performance of gene delivery when tested on different cell types," explained Tianyu Zhao, a PhD student in the Wang group and one of the main contributors to this work.
"An interesting characteristic of these polymer trees is that they can efficiently degrade into small branches and safely release the DNA inside the cell body. As a result, the cytotoxicity is significantly reduced and we can obtain a superior transfection profile in terms of both transfection capability and preservation of cell health," Tianyu explains.
Principal investigator, Dr Wenxin Wang said, "The versatility of our synthesis process could now allow us to tailor polymer properties, such as structure, functionality, strength, size, density and degradation with previously unimaginable ease. We hope this strategy towards highly branched degradable structures could open new avenues for the field of gene delivery."
Dr Wang’s research focuses on uncovering new therapies for diseases such as diabetic ulcers and epidermolysis bullosa (EB), which causes chronic skin fragility. This latest advancement in his polymer research is part of ongoing work to deliver the gene for type VII collagen to skin cells to help patients with recessive dystrophic epidermolysis bullosa.
"We are currently investigating the use of these new materials for biomedical applications such as drug/gene delivery, cross linkable hydrogel materials and skin adhesives. However, in reality this synthesis method could also be used for a wide range of materials outside the biomedical field."
The research is funded by Science Foundation Ireland, the Health Research Board and DEBRA Ireland.
Journal reference: Zhao, T., Zhang, H., Newland, B., Aied, A., Zhou, D., Wang, W.*. 'Significance of Branching for Transfection: Synthesis of Highly Branched Degradable Functional Poly(dimethylaminoethyl methacrylate) by Vinyl Oligomer Combination' Angewandte Chemie, 2014, doi:10.1002/ange.201402341R1 (accepted)