Evidence map›Paper›PMID 41131152›Full record

ArticleNature biotechnology2026

Elucidating lipid nanoparticle properties and structure through biophysical analyses.

Marshall S Padilla, Sarah J Shepherd, Andrew R Hanna, Martin Kurnik, Xujun Zhang, Michelle Chen, James Byrnes, Ryann A Joseph, Hannah M Yamagata, Adele S Ricciardi and 4 more

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Advancements in CRISPR-basedFrontiers in genome editing · 2026
    Review
  15. Drug Product Development of Lipid Nanoparticle-Based mRNA Therapeutics and Vaccines.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Marshall S PadillaDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-3607-790X
Sarah J ShepherdDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Andrew R HannaDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0009-3220-4378
Martin KurnikWaters Corporation, Goleta, CA, USA.ORCID http://orcid.org/0000-0001-9255-9730
Xujun ZhangWaters Corporation, Goleta, CA, USA.
Michelle ChenWaters Corporation, Goleta, CA, USA.
James ByrnesNational Synchrotron Light Source II, Brookhaven National Laboratory, Upton, NY, USA.
Ryann A JosephDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-0795-6094
Hannah M YamagataDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9525-7102
Adele S RicciardiDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-2637-8522
Kaitlin MrksichDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0008-7971-2129
David IssadoreDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-5461-8653
Kushol GuptaDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. kgupta@pennmedicine.upenn.edu.
Michael J MitchellDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA. mjmitch@seas.upenn.edu.ORCID http://orcid.org/0000-0002-3628-2244

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Designing lipid nanoparticle (LNP) delivery systems with specific targeting, potency and minimal side effects is crucial for their clinical use. However, traditional characterization methods, such as dynamic light scattering, cannot accurately quantify physicochemical properties of LNPs and how these are influenced by the lipid composition and mixing method. Here, we structurally characterize polydisperse LNP formulations by applying emerging solution-based biophysical methods that have higher resolution and provide biophysical data beyond size and polydispersity. These techniques include sedimentation velocity analytical ultracentrifugation, field-flow fractionation followed by multiangle light scattering and size-exclusion chromatography in line with synchrotron small-angle X-ray scattering. We show that LNPs have intrinsic polydispersity in size, RNA loading and shape, which depend on both the formulation technique and the lipid composition. Lastly, we predict LNP transfection in vitro and in vivo by examining the relationship between mRNA translation and physicochemical characteristics. Solution-based biophysical methods will be essential for determining LNP structure-function relationships, facilitating the creation of new design rules for LNPs.

Indexed as

LipidsNanoparticlesAnimalsChromatography, GelHumansParticle SizeScattering, Small AngleTransfectionUltracentrifugationLipids

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.