Evidence map›Paper›PMID 40998813›Full record

ArticleNature communications2025

Buffer optimization of siRNA-lipid nanoparticles mitigates lipid oxidation and RNA-lipid adduct formation.

Daniel A Estabrook, Lihua Huang, Olivia R Lucchese, Dylan J Charland, Zhao Yu, Fareed Bhasha Sayyed, Jonas Y Buser, Younghoon Oh, Xingyan Liu, Harmon A Johnson and 6 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Daniel A EstabrookLilly Seaport Innovation Center, Boston, MA, USA. estabrook_daniel@lilly.com.ORCID http://orcid.org/0000-0001-7237-6291
Lihua HuangEli Lilly and Company, Indianapolis, IN, USA.
Olivia R LuccheseLilly Seaport Innovation Center, Boston, MA, USA.ORCID http://orcid.org/0009-0009-3755-406X
Dylan J CharlandLilly Seaport Innovation Center, Boston, MA, USA.
Zhao YuEli Lilly and Company, Indianapolis, IN, USA.
Fareed Bhasha SayyedEli Lilly Services India Pvt Ltd., Bengaluru, India.
Jonas Y BuserEli Lilly and Company, Indianapolis, IN, USA.
Younghoon OhLilly Seaport Innovation Center, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2454-1701
Xingyan LiuLilly Seaport Innovation Center, Boston, MA, USA.
Harmon A JohnsonLilly Seaport Innovation Center, Boston, MA, USA.
Kenneth G RodriguezLilly Seaport Innovation Center, Boston, MA, USA.ORCID http://orcid.org/0009-0007-9444-5367
Noah A WamboltEurofins Lancaster Laboratories Professional Scientific Services, LLC, Lancaster, PA, USA.ORCID http://orcid.org/0009-0006-1453-6297
Sonia A CorbaEurofins Lancaster Laboratories Professional Scientific Services, LLC, Lancaster, PA, USA.ORCID http://orcid.org/0009-0007-0369-7762
Geoffrey T NashEli Lilly and Company, Indianapolis, IN, USA.ORCID http://orcid.org/0000-0002-1470-2279
Dennis YangEli Lilly and Company, Indianapolis, IN, USA.
Tingting WangEli Lilly and Company, Indianapolis, IN, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lipid nanoparticles are a versatile class of clinically approved drug delivery vehicles, particularly for nucleic acid cargoes. Despite this, these materials often suffer from instability issues that limit shelf-life or necessitate storage at ultra-cold temperatures. Herein, we demonstrate that the oxidation of unsaturated hydrocarbons within ionizable lipid tails results in the production of a dienone species that changes the conformation of the lipid tail and generates an electrophilic degradant that reacts with neighboring siRNA cargoes to produce siRNA-lipid adducts. This mechanism highlights the interplay between lipid degradation, colloidal instability, RNA-lipid adduct formation, and loss of bioactivity. In this work, we show that revised drug product matrixes, including mildly acidic, histidine-containing formulations, can improve room temperature stability of siRNA-lipid nanoparticles by mitigating these oxidative degradation mechanisms.

Indexed as

LipidsNanoparticlesRNARNA, Small InterferingBuffersHumansLiposomesOxidation-ReductionBuffersLipid NanoparticlesLipidsLiposomesRNARNA, Small Interfering

Identifiers

PMID40998813
PMCPMC12462517

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.