Aravind Asokan

Research: Synthetic virology and gene therapy

Aravind Asokan

Assistant Professor of Genetics, UNC-CH

Joint Appointment in Biochemistry and Biophysics

(PhD - University of North Carolina, Chapel Hill)

Gene Therapy Center CB#7352
5125 Thurston Bowles
Chapel Hill, NC 27599-7260

Asokan Lab Website


[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 (~ Wikipedia]

Adeno-Associated Virus (AAV) is a non-pathogenic, helper-depependent 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 AAV toolkit for the clinic. To achieve such, we utilize a broad spectrum of techniques and resources including gene synthesis, structural modeling, protein engineering, cell biology, microscopy, high throughput screening, genome editing tools and transgenic animal models.

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) integration of genome engineering tools with AAV vectors and (c) exploring the possibility whether viruses can package larger and/or structurally modified 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 and disassemble?  What receptors does AAV utilize to infect different cells? How do receptors interact with specific amino acid residues to form footprints on the capsid surface and how does this determine tissue tropism and antigenicity?  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, molecular and cell biology.

Applications: Natural and engineered AAV strains can be utilized in a broad spectrum of gene transfer applications. The first AAV-based gene therapy product - Glybera(r) has been approved in Europe and several others rapidly advancing in the pipeline. 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 biodistribution, toxicity and systemic transport mechanisms of AAV vectors in transgenic mouse models. Our ultimate goal is to generate lead candidates for gene therapy clinical trials.



(click for Full Publication List)

  • Optical control of CRISPR/Cas9 gene editing. Hemphill J, Borchardt EK et al. J Am Chem Soc. 2015 [link]
  • Unique glycan signatures regulate AAV tropism in the developing brain. Murlidharan G, Corriher T, Ghashghaei HT, Asokan A. J Virol. 2015. [link]
  • Functional analysis of the putative integrin recognition motif on adeno-associated virus 9. Shen et al., J Biol Chem. 2015. [link]
  • Biology of AAV vectors in the central nervous system. Murlidharan G, Samulski RJ, Asokan A. Front Mol Neurosci. 2014. [link]
  • Gene Therapy: Charting a Future Course - Summary a NIH Workshop. O'Reilly M et al., Hum Gene Ther. 2014. 35: 488-97. [link]
  • Preclinical toxicity evaluation of AAV for pain: evidence from human AAV studies and pharmacology of analgesic drugs. Pleitcha J et al. Mol Pain. 2014. 10:54. [link]
  • Cardiac I-1c overexpression with reengineered AAV vector improves cardiac function in swine ischemic heart failure. Ishikawa K et al., Mol Ther. 2014. Epub. [link]
  • An emerging AAV vector pipeline for cardiac gene therapy. Asokan A, Samulski RJ. 2013. 24(11): 906-913. [link]
  • Multiple roles for sialylated glycans in determining the cardiopulmonary tropism of adeno-associated virus 4.  Shen S, Troupes AN, Pulicherla N, Asokan A. J Virol. 2013. 87(24): 13206-13. [link]
  • 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. 288: 28814-23. [link]
  • 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. 87: 2994-3002. [link]
  • 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. 86: 10408-17. [link]
  • Single amino acid modification of AAV capsids changes transduction and humoral immune profiles. Li C, DiPrimio N, Bowles DE, Hirsch ML, Monahan PE, Asokan, Rabinowitz JE, Agbandje-McKenna M, Samulski RJ. J Virol. 2012. 86: 7752-9. [link]
  • Human Galectin 3 binding protein interacts with recombinant AAV serotype 6. Denard J, Beley C, Kotin R, Lai-Kuen R, Blot S, Leh H, Asokan A, Samulski RJ, Moullier P, Voit T, Garcia L, Svinartchouk F. J Virol. 2012. 86: 6620-31. [link]
  • Tyrosine Cross-Linking Reveals Interfacial Dynamics in Adeno-Associated Viral Capsids during Infection. Horowitz ED, Finn MG, Asokan A. ACS Chem Biol. 2012. 7: 1059-66. [link]
  • 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. [link]
  • Neutralizing antibodies against adeno-associated virus examined prospectively in pediatric patients with hemophilia. Li C, Narkbunnam N, Samulski, RJ, Asokan A, Monahan PE et al. Gene Ther. 2012. 19: 288-94. [link]
  • Bocavirus episome in infected human tissue contains non-identical termini. Kapoor A, Hornig M, Asokan A, Williams B, Henriquez JA, Lipkin WI. PLoS One. 2012. 6: e21362. [link]
  • The AAV vector toolkit: poised at the clinical crossroads. Asokan A, Schaffer DV, Samulski RJ. Mol Ther. 2012 Apr;20(4):699-708. [link]

Lab Contact: 

Lab Rooms: 513A Thurston Bowles
Lab Phone: 919-843-7622
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