Aravind Asokan

Michael Hirsch, PhD

Associate Professor
Department of Genetics and 
Department of Biochemistry & Biophysics 

 

 

 

 

 

Contact Info

UNC Gene Therapy Center
CB# 7352
Chapel Hill, NC 27599

Office: 5123 A Thurston Bowles Building
Phone: 919-843-7621
Fax: 919-843-7622
CV | Email

Research Interests

 "Parvovirus:: often truncated to “parvo” is both the common name in English casually applied to all the viruses in the Parvoviridae taxonomic family, and also the taxonomic name of the Parvovirus genus within the Parvoviridae family.  Parvoviruses are typically linear, non-segmented single-stranded DNA viruses, with an average genome size of 5,000 nucleotides.  Parvoviruses are some of the smallest viruses (from the latin word parvus, meaning small) and are 18-26 nm in diameter."   (~from Wikipedia, "Parvovirus")

Adeno-Associated Virus (AAV) is a member of the parvovirus family and currently being evaluated in human gene therapy clinical trials. We are interested in understanding the biology of AAV as well as developing a synthetic viral toolkit.

The AAV Genome: Manipulation of genomic material packaged within viruses is critical towards vector development for gene therapy applications.  Towards this end, we are interested in (a) incorporation of novel regulatory elements in viral vector genomes, (b) identification and mechanistic characterization of small molecules that impact viral gene expression and (c) exploring the possibility whether viruses can package chemically altered genomes.

The AAV Capsid: Among the smallest known viruses at a diameter of 25nm, the icosahedral AAV shell is comprised of 60 protein subunits and encapsidates a single-stranded DNA genome.  We are interested in understanding the biology of the AAV capsid at the molecular level. For instance, how does the capsid self-assemble?  How do changes in amino acid residues result in capsids with altered tissue tropism?  To answer these questions, we utilize an ever-expanding synthetic AAV toolkit generated through a combination of rational and combinatorial mutagenesis as well as new tools at the interface of chemistry and molecular biology.

Applications: Natural and engineered AAV strains can be utilized in a broad spectrum of gene transfer applications. We are currently developing vectors for therapeutic gene transfer in diseases affecting cardiac, pulmonary and neuromuscular organ systems. In conjunction with these efforts, we also carry out studies focused on systemic transport mechanisms of AAV vectors in transgenic mouse models. Our ultimate goal is to generate lead vector candidates for gene therapy clinical trials.

Publications

Multiple roles for sialylated glycans in determining the cardiopulmonary tropism of adeno-associated virus 4.  Shen S, Troupes AN, Pulicherla N, Asokan A. 2013 Sep 25.

Engraftment of a galactose receptor footprint onto adeno-associated viral capsids improves transduction efficiency. Shen S, Horowitz ED, Troupes AN, Brown SM, Pulicherla N, Samulski RJ, Agbandje-McKenna M, Asokan A. J Biol Chem. 2013 Aug 12.

Biophysical and ultrastructural characterization of adeno-associated viral capsid uncoating and genome release. Horowitz ED, Rahman KS, Bower BD, Dismuke DJ, Galvo MC, Griffith JD, Harvery SC, Asokan A. J Virol. 2012 Dec 26. 

Glycan binding avidity determines the systemic fate of adeno-associated virus 9. Shen S, Bryant K, Sun J, Brown S, Troupes A, Pulicherla N, Asokan A. J Virol. 2012. 

Tyrosine Cross-Linking Reveals Interfacial Dynamics in Adeno-Associated Viral Capsids during Infection. Horowitz ED, Finn MG, Asokan A. ACS Chem Biol. 2012 Apr 6.

Intra- and inter-subunit disulfide bond formation is nonessential in adeno-associated viral capsids. Pulicherla N, Kota P, Dokholyan NV, Asokan A. PLoS One. 2012;7(2):e32163. Epub 2012 Feb 28.

The AAV vector toolkit: poised at the clinical crossroads. Asokan A, Schaffer DV, Samulski RJ. Mol Ther. 2012 Apr;20(4):699-708.

Peptide Affinity Reagents for AAV Capsid Recognition and Purification. Nagesh Pulicherla and Aravind Asokan. Gene Ther. 2011. April 14. 

Glycated AAV Vectors: Chemical Redirection of Viral Tissue Tropism. Horowitz ED, Weinberg MS, Asokan A. Bioconjug Chem. 2011 March 9.

Engineering Liver-detargeted AAV9 Vectors for Cardiac and Musculoskeletal Gene Transfer.Pulicherla N, Shen S, Yadav S, Debbink K, Govindasamy L, Agbandje-McKenna M, Asokan A. Mol Ther. 2011 March 1. 

Terminal N-linked galactose is the primary receptor for adeno-associated virus 9Shen Shen, Kelli D. Byrant, Sarah M. Brown, Scott H. Randell  Aravind Asokan. J Biol Chem. 2011 March 2.

Reengineered AAV vectors: old dog, new tricks. Aravind Asokan.  Discov Med. 2010 May 9.

Reengineering a receptor footprint of adeno-associated virus enables selective and systemic gene transfer to muscle. Asokan A, Conway JC, Phillips JL, Li C, Hegge J, Sinnott R, Yadav S, DiPrimio N, Nam HJ, Agbandje-McKenna M, McPhee S, Wolff J, Samulski RJ. Nat Biotechnol. 2010 Jan 28.

 

For publications prior to 2010, click below – uses pubmed image

http://www.ncbi.nlm.nih.gov/pubmed?term=asokan%20a