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

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.”

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.

add to favorites email to friend print save as pdf

Related Stories

Image pinpoints all 5 million atoms in viral coat

Feb 16, 2009

(PhysOrg.com) -- If a picture is worth a thousand words, then Rice University's precise new image of a virus' protective coat is seriously undervalued. More than three years in the making, the image contains ...

Recommended for you

A nucleotide change could initiate fragile X syndrome

20 hours ago

Researchers reveal how the alteration of a single nucleotide—the basic building block of DNA—could initiate fragile X syndrome, the most common inherited form of intellectual disability. The study appears ...

Gene clues to glaucoma risk

Aug 31, 2014

Scientists on Sunday said they had identified six genetic variants linked to glaucoma, a discovery that should help earlier diagnosis and better treatment for this often-debilitating eye disease.

Mutation disables innate immune system

Aug 29, 2014

A Ludwig Maximilian University of Munich team has shown that defects in the JAGN1 gene inhibit the function of a specific type of white blood cells, and account for a rare congenital immune deficiency that ...

Study identifies genetic change in autism-related gene

Aug 28, 2014

A new study from Bradley Hospital has identified a genetic change in a recently identified autism-associated gene, which may provide further insight into the causes of autism. The study, now published online in the Journal of ...

NIH issues finalized policy on genomic data sharing

Aug 27, 2014

The National Institutes of Health has issued a final NIH Genomic Data Sharing (GDS) policy to promote data sharing as a way to speed the translation of data into knowledge, products and procedures that improve health while ...

User comments