4.4 Article

Characterization of Interactions between Heparin/Glycosaminoglycan and Adeno-Associated Virus

期刊

BIOCHEMISTRY
卷 52, 期 36, 页码 6275-6285

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AMER CHEMICAL SOC
DOI: 10.1021/bi4008676

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资金

  1. National Institutes of Health [GM-38060, GM66875]
  2. Pilot Project Grant from the Oregon Health & Science University Center for Spatial Systems Biomedicine
  3. Interactions at Microbe-Host Interface training grant from the National Institutes of Health [T32AI007472]

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Adeno-associated virus (AAV) is a key candidate in the development of gene therapy. In this work, we used surface plasmon resonance spectroscopy to study the interaction between AAV and heparin and other glycosaminoglycans (GAGs). Surface plasmon resonance results revealed that heparin binds to AAV with an extremely high affinity. Solution competition studies showed that binding of AAV to heparin is chain length dependent AAV prefers to bind full la chain heparin. All sulfo groups (especially N-sulfo and 6-O-sulfo groups) on heparin are important for the AAV heparin interaction. Higher levels of sulfo group substitution in GAGs enhance their binding affinities. Atomic force microscopy was also performed to image AAV-2 in a complex with heparin.

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