Evidence map›Paper›PMID 29721534›Full record

ArticleACS central science2018

Machine Learning To Predict Cell-Penetrating Peptides for Antisense Delivery.

Justin M Wolfe, Colin M Fadzen, Zi-Ning Choo, Rebecca L Holden, Monica Yao, Gunnar J Hanson, Bradley L Pentelute

Open access · diamondAbstract read
In one paragraph

Article in ACS central science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

39 citing papers in PubMed, 84 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
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  6. Article
  7. Article
  8. Article
  9. Dynamic carriers for therapeutic RNA delivery.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Can pulmonary RNA delivery improve our pandemic preparedness?Journal of controlled release : official journal of the Controlled Release Society · 2022
    Article
  17. Article
  18. Biological Membrane-Penetrating Peptides: Computational Prediction and Applications.Frontiers in cellular and infection microbiology · 2022
    Review
  19. Synthetic Molecular Evolution of Cell Penetrating Peptides.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  20. Cell-Penetrating Peptides.Methods in molecular biology (Clifton, N.J.) · 2022
    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

7 authors at 2 institutions in 1 country.

Justin M WolfeDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Colin M FadzenDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Zi-Ning ChooDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Rebecca L HoldenDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Monica YaoResearch Chemistry, Sarepta Therapeutics, Inc., Cambridge, Massachusetts, United States.
Gunnar J HansonResearch Chemistry, Sarepta Therapeutics, Inc., Cambridge, Massachusetts, United States.
Bradley L PenteluteDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Massachusetts Institute of Technology · USSarepta Therapeutics (United States) · US

Funding

Chemically Modified Peptide Agents for Next-Generation Conjugate Therapies to Treat Duchenne Muscular DystrophyF30HD093358 · NICHD · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI FADZEN, COLIN MACLAINE · 2017 to 2019
$142k
NICHD NIH HHS F30 HD093358
6 · The paper itself

Abstract

Cell-penetrating peptides (CPPs) can facilitate the intracellular delivery of large therapeutically relevant molecules, including proteins and oligonucleotides. Although hundreds of CPP sequences are described in the literature, predicting efficacious sequences remains difficult. Here, we focus specifically on predicting CPPs for the delivery of phosphorodiamidate morpholino oligonucleotides (PMOs), a compelling type of antisense therapeutic that has recently been FDA approved for the treatment of Duchenne muscular dystrophy. Using literature CPP sequences, 64 covalent PMO-CPP conjugates were synthesized and evaluated in a fluorescence-based reporter assay for PMO activity. Significant discrepancies were observed between the sequences that performed well in this assay and the sequences that performed well when conjugated to only a small-molecule fluorophore. As a result, we envisioned that our PMO-CPP library would be a useful training set for a computational model to predict CPPs for PMO delivery. We used the PMO activity data to fit a random decision forest classifier to predict whether or not covalent attachment of a given peptide would enhance PMO activity at least 3-fold. To validate the model experimentally, seven novel sequences were generated, synthesized, and tested in the fluorescence reporter assay. All computationally predicted positive sequences were positive in the assay, and one sequence performed better than 80% of the tested literature CPPs. These results demonstrate the power of machine learning algorithms to identify peptide sequences with particular functions and illustrate the importance of tailoring a CPP sequence to the cargo of interest.

Identifiers

PMID29721534
PMCPMC5920612
OpenAlexW2796024961

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.