Evidence map›Paper›PMID 34109242›Full record

ArticleERJ open research2021

Anti-HSP47 siRNA lipid nanoparticle ND-L02-s0201 reverses interstitial pulmonary fibrosis in preclinical rat models.

Yun Liu, Jian Liu, Alistair Quimbo, Fengcheng Xia, Jiping Yao, Jean-Pierre Clamme, Sonya Zabludoff, Jun Zhang, Wenbin Ying

Open access · goldAbstract read
In one paragraph

Article in ERJ open research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
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

23 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
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  7. Around the collagen triple helix: an introduction to studying associated genetic and acquired diseases.Matrix biology : journal of the International Society for Matrix Biology · 2025
    Review
  8. Treatment of lung diseasesMaterials today. Bio · 2025
    Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Recent advances in nanoparticulate RNA delivery systems.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  14. Therapeutic potential for renal fibrosis by targeting Smad3-dependent noncoding RNAs.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Review
  15. The landscape of nanoparticle-based siRNA delivery and therapeutic development.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Review
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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

9 authors at 1 institution in 1 country.

Yun LiuNitto Biopharma Inc., San Diego, CA, USA.
Jian LiuNitto Biopharma Inc., San Diego, CA, USA.
Alistair QuimboNitto Biopharma Inc., San Diego, CA, USA.
Fengcheng XiaNitto Biopharma Inc., San Diego, CA, USA.
Jiping YaoNitto Biopharma Inc., San Diego, CA, USA.
Jean-Pierre ClammeNitto Biopharma Inc., San Diego, CA, USA.
Sonya ZabludoffNitto Biopharma Inc., San Diego, CA, USA.
Jun ZhangCellagen Technology, San Diego, CA, USA.
Wenbin YingNitto Biopharma Inc., San Diego, CA, USA.
Nitto (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

ND-L02-s0201 is a lipid nanoparticle encapsulating an siRNA which inhibits expression of heat shock protein 47 (HSP47), a collagen-specific chaperone. Accumulated evidence demonstrates a close association between increased level of HSP47 and excessive accumulation of collagen in fibrotic diseases. Our objective was to test ND-L02-s0201 efficacy in preclinical lung fibrosis models and characterise the downstream histological and functional consequences of inhibiting the expression of HSP47. Comprehensive optimisation and characterisation of bleomycin (BLM) and silica-induced rat lung fibrosis models were conducted, which ensured progressive pathological changes were sustained throughout the study during evaluation of the anti-fibrotic potential of ND-L02-s0201. In the BLM model, we demonstrated dose-dependent and statistically significant reduction in the relative lung weight, collagen deposition and histology, and fibrosis scores following ND-L02-s0201 treatment. Lung tissue mRNA profiling demonstrated that 11 out of 84 fibrosis-relevant genes were upregulated following BLM induction and were downregulated by approximately 4.5-fold following ND-L02-s0201 treatment. Epithelial-mesenchymal transition was characterised in the BLM model following ND-L02-s0201 treatment. Cell enrichment demonstrated that myofibroblasts contained the highest HSP47 mRNA expression. BLM led to more than a five-fold increase in myofibroblasts and ND-L02-s0201 treatment reduced the myofibroblasts to sham levels. Statistically significant improvement in lung function was noted in the BLM model which was determined by running endurance capacity using a 7-minute treadmill test. Comparable anti-fibrotic efficacy was also observed in the silica model. Results from two robust chronic rodent models of pulmonary fibrosis demonstrated significant anti-fibrotic effects and improved lung function which support the evaluation of ND-L02-s0201 in subjects with idiopathic pulmonary fibrosis.

Identifiers

PMID34109242
PMCPMC8181707
OpenAlexW3130635287

What OpenQuestion holds

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Registered trials

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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.