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High resolution ES-DMA quantifies AAV capsid DNA content by electrical mobility to mass correlation.

Preston Dennett1, Lohra M Young2, Benjamin E Draper2

  • 1NanoEngineering Corporation, New Haven, CT, USA.

Gene Therapy
|June 4, 2026
PubMed
Summary

High-resolution electrospray differential mobility analysis (ES-DMA) accurately sizes recombinant adeno-associated virus (rAAV) particles. This novel method distinguishes empty, full, and partial rAAV capsids, improving gene therapy manufacturing quality control.

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Area of Science:

  • Biotechnology
  • Analytical Chemistry
  • Molecular Biology

Background:

  • Recombinant Adeno-Associated Virus (rAAV) is a key viral vector for gene therapy.
  • Accurate assessment of rAAV DNA content is crucial for manufacturing and quality control.
  • Impurities like empty or over-filled capsids reduce efficacy and increase patient risk.

Purpose of the Study:

  • Introduce high-resolution electrospray differential mobility analysis (ES-DMA) for rAAV characterization.
  • Demonstrate ES-DMA's ability to resolve DNA encapsidation in rAAV particles.
  • Benchmark ES-DMA against charge detection mass spectrometry (CD-MS).

Main Methods:

  • Utilized high-resolution electrospray differential mobility analysis (ES-DMA).
  • Analyzed microliter volumes of rAAV samples.
  • Compared ES-DMA results with charge detection mass spectrometry (CD-MS).

Main Results:

  • ES-DMA provides angstrom-scale particle sizing sufficient for resolving rAAV DNA encapsidation.
  • A strong near-linear correlation was found between electrical mobility and mass of aerosolized rAAV particles.
  • ES-DMA enables rapid identification and quantification of empty, full, and partial/over-filled rAAV capsids.

Conclusions:

  • ES-DMA is a novel, effective benchtop analytical method for rAAV vector characterization.
  • This technique can improve the quality control of gene therapy vectors.
  • ES-DMA offers a viable alternative for assessing rAAV capsid content.