Evidence map›Paper›PMID 33802146›Full record

ArticleBiomolecules2021

Actin-Resistant DNase1L2 as a Potential Therapeutics for CF Lung Disease.

Danila Delfino, Giulia Mori, Claudio Rivetti, Antonella Grigoletto, Gloria Bizzotto, Cristian Cavozzi, Marco Malatesta, Davide Cavazzini, Gianfranco Pasut, Riccardo Percudani

Open access · goldAbstract read
In one paragraph

Article in Biomolecules, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

17 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Research Progress on the Mechanisms of High Mucus Secretion in the Airway: A Scoping Review.International journal of chronic obstructive pulmonary disease · 2026
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
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

10 authors at 2 institutions in 1 country.

Danila DelfinoDepartment of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy.ORCID 0000-0002-6835-6367
Giulia MoriDepartment of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy.
Claudio RivettiDepartment of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy.
Antonella GrigolettoDepartment of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy.ORCID 0000-0001-9679-0083
Gloria BizzottoDepartment of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy.
Cristian CavozziDepartment of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy.ORCID 0000-0001-6472-1403
Marco MalatestaDepartment of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy.ORCID 0000-0001-5668-0787
Davide CavazziniDepartment of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy.
Gianfranco PasutDepartment of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy.ORCID 0000-0002-8754-0899
Riccardo PercudaniDepartment of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy.ORCID 0000-0001-8452-1062
University of Parma · ITUniversity of Padua · IT

Funding

Fondazione per la Ricerca sulla Fibrosi Cistica FFC#9/2018
6 · The paper itself

Abstract

In cystic fibrosis (CF), the accumulation of viscous lung secretions rich in DNA and actin is a major cause of chronic inflammation and recurrent infections leading to airway obstruction. Mucolytic therapy based on recombinant human DNase1 reduces CF mucus viscosity and promotes airway clearance. However, the marked susceptibility to actin inhibition of this enzyme prompts the research of alternative treatments that could overcome this limitation. Within the human DNase repertoire, DNase1L2 is ideally suited for this purpose because it exhibits metal-dependent endonuclease activity on plasmid DNA in a broad range of pH with acidic optimum and is minimally inhibited by actin. When tested on CF artificial mucus enriched with actin, submicromolar concentrations of DNase1L2 reduces mucus viscosity by 50% in a few seconds. Inspection of superimposed model structures of DNase1 and DNase1L2 highlights differences at the actin-binding interface that justify the increased resistance of DNase1L2 toward actin inhibition. Furthermore, a PEGylated form of the enzyme with preserved enzymatic activity was obtained, showing interesting results in terms of activity. This work represents an effort toward the exploitation of natural DNase variants as promising alternatives to DNase1 for the treatment of CF lung disease.

Indexed as

ActinsAmino Acid SequenceCalciumCatalytic DomainConserved SequenceCysteineCystic FibrosisDeoxyribonuclease IDNAHumansMucusOxidation-ReductionPichiaPlasmidsPolyethylene GlycolsProtein BindingActinsCalciumCysteineDeoxyribonuclease IDNADNASE1L2 protein, humanPolyethylene GlycolsRecombinant Proteinscystic fibrosisendonucleaseenzyme therapeuticsmucolyticsPEGylationPichia pastoris

Identifiers

PMID33802146
PMCPMC8002113
OpenAlexW3135807510

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.