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Editorial
. 2021 Feb 11;137(6):721-723.
doi: 10.1182/blood.2020009285.

No CpGs for AAVs?

Lindsey A George  1
Affiliations
Editorial

No CpGs for AAVs?

Lindsey A George. Blood. .

Abstract

In this issue of Blood, Konkle et al report that 7 of 8 participants in a phase 1/2 trial of adeno-associated virus (AAV) vector (BAX335) for factor IX (FIX)-Padua gene transfer in patients with hemophilia B did not maintain expression despite steroid intervention, which the authors hypothesize is a result of the innate immune stimulatory effect of CpG motifs enriched within their vector cassette. Their study demonstrates that the cellular immune response to AAV vectors does not always respond to steroids and provides insight into mechanisms that may contribute to the AAV immune response with implications for the future design of AAV vectors.

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Conflict of interest statement

Conflict-of-interest disclosure: L.A.G. has been a consultant for Pfizer and Bayer, serves on the data monitoring committee of Avrobio, and is a clinical investigator for phase 1/2 hemophilia A and B gene therapy trials sponsored by Spark Therapeutics and Pfizer, respectively.

Conflict-of-interest disclosure: L.A.G. has been a consultant for Pfizer and Bayer, serves on the data monitoring committee of Avrobio, and is a clinical investigator for phase 1/2 hemophilia A and B gene therapy trials sponsored by Spark Therapeutics and Pfizer, respectively.

Comment on

References

    1. Konkle BA, Walsh CE, Escobar MA, et al. BAX 335 hemophilia B gene therapy clinical trial results: potential impact of CpG sequences on gene expression. Blood. 2021;137(6):763-774. - PMC - PubMed
    1. Manno CS, Pierce GF, Arruda VR, et al. Successful transduction of liver in hemophilia by AAV-factor IX and limitations imposed by the host immune response. Nat Med. 2006;12(3):342-347. - PubMed
    1. Mingozzi F, Maus MV, Hui DJ, et al. CD8(+) T-cell responses to adeno-associated virus capsid in humans. Nat Med. 2007;13(4):419-422. - PubMed
    1. Nathwani AC, Tuddenham EG, Rangarajan S, et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med. 2011;365(25):2357-2365. - PMC - PubMed
    1. George LA, Sullivan SK, Giermasz A, et al. Hemophilia B gene therapy with a high-specific-activity factor IX variant. N Engl J Med. 2017;377(23):2215-2227. - PMC - PubMed

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