Researchers determine 3D structure of adeno-associated virus 9: Aim to boost gene therapy

June 21, 2012

A team of researchers led by the University of Florida, Gainesville, has determined the precise structure of a virus that has promise as a delivery vehicle for gene therapy. The research appears in the June 2012 issue of the Journal of Virology.

Adeno-associated viruses are benign in humans, and are highly promising in as delivery devices to place healthy into the , in order to compensate for malfunctioning genes. These viruses come in 12 different serotypes (sets of antigens). Adeno-associated virus 9 (AAV9) is currently under development as a for treating , such as spinal muscle atrophy, amyotrophic lateral sclerosis, and Parkinson’s disease.

Mavis Agbandje-McKenna of the University of Florida, Gainesville and her colleagues have determined the precise structure of AAV9, work she says “will help us to understand which parts of the capsid we can alter or modify to make safer, more efficient vectors, and which regions should not be modified as we try to engineer capsids to treat specific diseases.” The capsid is the shell that protects the viral nucleic acid.

The researchers applied X-ray crystallography, the technique that was used to determine DNA’s structure nearly 60 years ago, as well as a complementary, and much newer technique called cryo-electron microscopy and image reconstruction, to determining AAV9’s structure. That work revealed the precise position in space of every atom of the AAV9 capsid. They then compared that structure to other adeno-associated for which structures have been determined, and identified which regions are conserved, and which vary, in comparison to AAV9. They then annotated these regions with respect to function: different parts of the capsid are involved in different functions such as receptor attachment, determining the efficiency of transduction in specific tissues, and antibody recognition.

“Our goal is to use 3D information to inform the design of gene delivery vectors that will have improved efficacy with respect to tissue targeted delivery of therapies, and reduced host immune antibody response recognition,” says Agbandje-McKenna. “The information that we have obtained is guiding further research in our group as well as groups elsewhere who are trying to understand the functions of the capsid, in an effort to improve gene delivery via AAV.” She notes that AAV9 is especially important in these areas because of its ability to cross the blood brain barrier, adding that this makes it particularly useful for treating brain diseases, “for which current therapies are quite limited.”

Explore further: Gene therapy success depends on ability to advance viral delivery vectors to commercialization

More information: M.A. DeMattia, H.-J. Nam, K. Van Vliet, M. Agbandje-McKenna, et al. Structural insight into the unique properties of adeno-associated virus serotype 9. J. Virol. 86:6947-6958.

Related Stories

Gene therapy success depends on ability to advance viral delivery vectors to commercialization

May 18, 2011
Many gene therapy strategies designed to deliver a normal copy of a gene to cells carrying a disease-causing genetic mutation rely on a modified virus to transfer the gene product into affected tissues. One technology platform ...

Can nerve growth factor gene therapy prevent diabetic heart disease?

December 20, 2011
Diabetes is a major risk factor for cardiovascular disease and can reduce blood supply to the heart tissue and damage cardiac cells, resulting in heart failure. New research has investigated if nerve growth factor (NGF) gene ...

Recommended for you

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly identified genetic marker may help detect high-risk flu patients

July 17, 2017
Researchers have discovered an inherited genetic variation that may help identify patients at elevated risk for severe, potentially fatal influenza infections. The scientists have also linked the gene variant to a mechanism ...

0 comments

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.