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Viral receptors and vector purification: New approaches for generating clinical-grade reagents

Nature Medicine volume 5, pages 587–588 (1999)Cite this article

Many viral vectors have shown promise as gene delivery systems in small-animal studies1. As these vectors progress to the next level of phase I and phase II clinical studies, it is important to establish vector purification schemes that are both amenable to large-scale production and that meet the rigorous regulations of the US Food and Drug Administration. At a recent meeting on viral vector purification held in Williamsburg, Virginia, emphasis was placed on the need to move away from purification strategies that use potentially toxic reagents (that is, CsCl). Discussions focused on the development of new strategies that are more benign, such as column chromatographic procedures2. Most companies have already moved away from the conventional academic procedures, which use CsCl density centrifugation, and are purifying viral vectors by column chromatography with ion-exchange and/or size-exclusion columns. Although these procedures achieve their goal, the methods are often less efficient than ligand affinity matrix chromatography. The use of an affinity matrix composed of a natural viral receptor or a high-affinity antibody is a much more specific medium for separating viral vectors from host cellular proteins.

Immuno-affinity chromatography

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Figure 1: Heparan sulfate proteoglycan is a receptor for AAV-2 virions.
Figure 2: New strategies for purification of AAV vector.

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Authors and Affiliations

  1. Gene Therapy Center, 7119 Thurston-Bowles, CB 7352, Chapel Hill, 27599, North Carolina, USA

    Candace Summerford & Richard Jude Samulski

  2. Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, 27599, North Carolina, USA

    Candace Summerford & Richard Jude Samulski

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  1. Candace Summerford
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  2. Richard Jude Samulski
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Correspondence to Richard Jude Samulski.

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Summerford, C., Samulski, R. Viral receptors and vector purification: New approaches for generating clinical-grade reagents. Nat Med 5, 587–588 (1999). https://doi.org/10.1038/8470

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