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<p>Advanced biophysical characterization techniques are essential for accelerating the development of emerging modalities such as lipid nanoparticle (LNP) vaccines and liposome adjuvants through elucidation of morphological features linked to critical quality attributes (CQAs). Cryogenic electron microscopy (cryo-EM) is widely employed to assess liposome lamellarity and LNP morphology but it is costly and time-consuming regarding instrumentation, sample preparation and data collection. Small Angle X-ray Scattering (SAXS) offers complementary size and shape information of biomolecules in solution with higher throughput, especially when combined with robotics-enabled automated sampling. Our study is to build a correlation between SAXS and cryo-EM and enable SAXS to serve as a rapid screening tool in vaccine formulation development. To develop an integrated biophysical toolbox for expedited structural characterization, we correlated cryo-EM images and SAXS profiles of liposomes and LNPs made using different conditions during process development (e.g. extrusion passes, microfluidic mixing methods). The correlations between SAXS and cryo-EM were established in the lamellarity assessment for liposomes and morphology for LNPs. Our study demonstrated that SAXS profiles alone can reliably and rapidly inform process and formulation development, reducing the need for cryo-EM imaging of intermediate samples. Establishing a robust correlation between cryo-EM and SAXS enabled faster turnaround in addressing critical process and formulation questions for liposomes and LNPs, thereby streamlining vaccine development workflows.</p> Graphical Abstract <p></p>

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Adding to the pharmaceutical analytical toolbox for liposome and lipid nanoparticle characterization: correlating Small Angle X-ray Scattering (SAXS) and Cryo-EM imaging

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月6日

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  • Suzette Pabit,
  • Irene Yin-Ting Chang,
  • Donald Kotowski Jr.,
  • Sudipta Gupta,
  • Shailaa Kummar,
  • Milan Ghodasara,
  • Jian Xiong,
  • Jeffrey Smith,
  • Lauren Austin,
  • Courtney David,
  • David Boyd,
  • Mingzhang Maple Wang,
  • Michael J. McNevin,
  • Malini Mukherjee,
  • Christopher J. Farrell

摘要

Advanced biophysical characterization techniques are essential for accelerating the development of emerging modalities such as lipid nanoparticle (LNP) vaccines and liposome adjuvants through elucidation of morphological features linked to critical quality attributes (CQAs). Cryogenic electron microscopy (cryo-EM) is widely employed to assess liposome lamellarity and LNP morphology but it is costly and time-consuming regarding instrumentation, sample preparation and data collection. Small Angle X-ray Scattering (SAXS) offers complementary size and shape information of biomolecules in solution with higher throughput, especially when combined with robotics-enabled automated sampling. Our study is to build a correlation between SAXS and cryo-EM and enable SAXS to serve as a rapid screening tool in vaccine formulation development. To develop an integrated biophysical toolbox for expedited structural characterization, we correlated cryo-EM images and SAXS profiles of liposomes and LNPs made using different conditions during process development (e.g. extrusion passes, microfluidic mixing methods). The correlations between SAXS and cryo-EM were established in the lamellarity assessment for liposomes and morphology for LNPs. Our study demonstrated that SAXS profiles alone can reliably and rapidly inform process and formulation development, reducing the need for cryo-EM imaging of intermediate samples. Establishing a robust correlation between cryo-EM and SAXS enabled faster turnaround in addressing critical process and formulation questions for liposomes and LNPs, thereby streamlining vaccine development workflows.

Graphical Abstract