Last Updated: 9/3/2009

Research Interests
Viruses are remarkably plastic entities. New strains evolve constantly driven by genetic drift and iterative mutagenesis. Acceleration of these evolutionary processes in a laboratory setting will greatly impact our ability to carry out studies focused on understanding molecular mechanisms underlying viral infection. The overarching goal of my lab is to combine the tools and principles of molecular biology and genetics with chemistry to generate a synthetic viral toolkit. The resulting hybrid viral entities are utilized to unravel viral infectious pathways, provide novel vectors for gene therapy and reagents for molecular genetics applications.

The Adeno-Associated Virus (AAV) Capsid
AAV is a non-pathogenic member of the Parvoviridae family that is rapidly gaining popularity as a vector for gene transfer. 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.

The Lentiviral Envelope
The Lentivirus (e.g., HIV), a genus of the Retroviridae family, is another popular tool for gene transfer applications. The spherical virions are enveloped with lipids derived from host cell membranes and package an RNA genome. Using metabolic engineering tools, we are interested in manipulating molecular components of the lentiviral envelope to generate a synthetic lentiviral panel for mechanistic studies and gene therapy applications.

The Viral 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.

Our long term goal is to develop new lab-derived viral vector strains ideal for translational studies in areas including genetic disorders, infectious disease and cancer.

Publications
1. Asokan A (Corresponding Author), Phillips J, Conway, J, Li C, Hegge J, Yadav S, DiPrimio N, Nam HJ,
Agbandje-McKenna M, Wolff JA, Samulski RJ. Re-engineering Receptor Footprints on AAV Capsids Yields
Synthetic Vectors with Unique Tissue Tropisms. (Submitted)
2. Aravind Asokan, Chengwen Li, Jarrod Johnson and R.J.Samulski. 2008. Bioluminescent virion shells: New
tools for quantitation of AAV vector dynamics in cells and live animals. Gene Therapy. 15(24):1618-22.
3. Wuping Li, Aravind Asokan, Zhijian Wu, Van Dyke T, R.J.Samulski et al. 2008. Engineering and selection of
shuffled AAV genomes: a new strategy for producing targeted biological nanoparticles. Molecular Therapy.
16(7):1252-60.
4. Nina DiPrimio, Aravind Asokan, Lakshmanan Govindasamy, Mavis Agbandje-McKenna, and R. J. Samulski.
2008. Surface loop dynamics in adeno-associated virus capsid assembly. J Virol. 82(11):5178-89.
5. Vivian Choi, Aravind Asokan, Rebecca Haberman, and R.J.Samulski. 2007. Production of recombinant AAV
vectors. Current Protocols in Molecular Biology. Cpt. 16, Unit 16.25.
6. Zhijian Wu, Aravind Asokan, Joshua Grieger, Lakshmanan Govindasamy, Mavis Agbandje-McKenna and
R.J.Samulski. 2006. Single amino acid changes can influence titer, heparin binding, and liver tropism in
different adeno-associated virus (AAV) serotypes. J. Virol. 80(22): 11393-11397.
7. Zhijian Wu, Aravind Asokan, and R.J.Samulski. 2006. Adeno-associated virus serotype vectors: A versatile
toolkit for human gene therapy. Molecular Therapy. 14(3): 316-327.
8. Aravind Asokan, J.B.Hamra, M. Agbandje-McKenna, and R.J.Samulski. 2006. Adeno-associated virus type 2
contains an integrin α5β1-binding domain essential for viral cell entry. J. Virol. 80(18): 8961-8969.
9. Aravind Asokan and R.J.Samulski. 2006. AAV does the shuffle. 2006. Nat Biotech. 24(2): 158-160.
10. Aravind Asokan and R.J.Samulski. 2005. From crystal structure to clinic: Highlights of the tenth international
parvovirus workshop. Molecular Therapy. 11(5): 656-660.

E-mail: ARAVIND@MED.UNC.EDU
Telephone: 843-7621/7622
FAX: 966-0907
Address: Thurston Building, Rm. 4101 , NC

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