NA-CDQuant: Quantitative spectral analysis of nucleic acid structure by circular dichroism spectroscopy.

Authors

Kevin Mosca, Søren Vrønning Hoffmann, Nykola C Jones, Richard R Sinden, Frank Wien, Sergio Marco, Véronique Arluison

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 41. Pages e2617882123. Oct 13, 2026. Epub Oct 06, 2026.

Abstract

Understanding the structural conformation and dynamics of nucleic acids in solution is critical for the development of nucleic acid therapeutics involving antisense or mRNA therapies, where controlling stability, efficacy, and manufacturability are important. Circular dichroism (CD) spectroscopy allows rapid and nondestructive solution analysis of the spatial arrangements of nucleic acids. While widely used to analyze protein structure, the potential of CD for DNA- and RNA-based pharmaceutical applications has remained largely unrealized because nucleic acid spectra are complex and difficult to interpret quantitatively. We introduce herein a framework (NA-CDQuant) that transforms CD from a qualitative fingerprinting method into a quantitative tool for nucleic acid structure prediction by combining spectral deconvolution with a rigorously curated synchrotron radiation circular dichroism reference library comprising 18 structurally defined conformational families. This systematic classification overcomes long-standing challenges posed by spectral overlap and structural polymorphism, enabling estimation of the fractional composition of coexisting conformations during real-time monitoring of structural transitions in solution. NA-CDQuant provides mechanistic insight into subtle conformational redistributions that may affect molecular recognition and functional performance assisting pharmaceutical development and medical application by facilitating formulation optimization, stability assessment, quality control, and regulatory support of nucleic acid-based therapeutics.

PMID:
42837461
Bibliographic data and abstract were imported from PubMed on 07 Oct 2026.

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