Evidence map›Paper›PMID 26025036›Full record

ReviewBiotechnology advances2015

A role for peptides in overcoming endosomal entrapment in siRNA delivery - A focus on melittin.

Kirk K Hou, Hua Pan, Paul H Schlesinger, Samuel A Wickline

Abstract readReview
In one paragraph

Review in Biotechnology advances, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 8% 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

44 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.

  1. Pooled it
  2. 3D Printing and Electrospinning of PLLA-ACS biomaterials science & engineering · 2026
    Article
  3. Bacterial Foreignization Nanosystem Elicits Multi-Phenotypic T Cells for Antitumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Nanoparticle-Based Chimeric Antigen Receptor Therapy for Cancer Immunotherapy.Tissue engineering and regenerative medicine · 2023
    Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. mRNA nanomedicine: Design and recent applications.Exploration (Beijing, China) · 2022
    Review
  16. Review
  17. Article
  18. Article
  19. New approaches to moderate CRISPR-Cas9 activity: Addressing issues of cellular uptake and endosomal escape.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Review
  20. 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

4 authors at 1 institution in 1 country.

Kirk K HouComputational and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63108, USA.
Hua PanDepartment of Medicine, Washington University School of Medicine, St Louis, MO 63108, USA.
Paul H SchlesingerDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63108, USA.
Samuel A WicklineDepartment of Medicine, Washington University School of Medicine, St Louis, MO 63108, USA; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO 63108, USA. Electronic address: saw@wuphys.wustl.edu.
Washington University in St. Louis · US

Funding

METHODS IN MOLECULAR IMAGING AND TARGETED THERAPEUTICSR01HL073646 · NHLBI · WASHINGTON UNIVERSITY · PI WICKLINE, SAMUEL A · 2004 to 2016
$13.7M
Translational Insights into Estrogen Receptor alpha-Positive Luminal Breast CanceU01CA141541 · NCI · WASHINGTON UNIVERSITY · PI CARDIFF, ROBERT D, SCHREIBER, ROBERT DAVID · 2009 to 2013
$3.8M
Prevention and Treatment of Acute Kidney InjuryR01DK102691 · NIDDK · WASHINGTON UNIVERSITY · PI WICKLINE, SAMUEL A · 2015 to 2018
$2.0M
Inhibition of NF-kB with siRNA/Peptide Nanoparticles for Arthritis TreatmentR01AR067491 · NIAMS · WASHINGTON UNIVERSITY · PI PHAM, CHRISTINE T., WICKLINE, SAMUEL A · 2015 to 2019
$1.8M
THERAPY NANOPARTICLES FOR MODULATION OF INFLAMMATION IN NEUROMUSCULAR DISEASER01AR056223 · NIAMS · WASHINGTON UNIVERSITY · PI WICKLINE, SAMUEL A · 2009 to 2013
$1.6M
ENTROPY-BASED TISSUE DISCRIMINATORSR21EB018095 · NIBIB · WASHINGTON UNIVERSITY · PI WICKLINE, SAMUEL A · 2013 to 2014
$412k
QUANTIFYING KIDNEY INJURY AND INFLAMMATION WITH FLUORINE (19F) MRIR21DK095555 · NIDDK · WASHINGTON UNIVERSITY · PI WICKLINE, SAMUEL A · 2012 to 2013
$411k
NCI NIH HHS U01 CA141541NHLBI NIH HHS R01 HL073646NHLBI NIH HHS R01 HL073646-08NIAMS NIH HHS R01 AR056223NIAMS NIH HHS R01 AR067491NIBIB NIH HHS R21 EB018095NIDDK NIH HHS R01 DK102691NIDDK NIH HHS R21 DK095555
6 · The paper itself

Abstract

siRNA has the possibility to revolutionize medicine by enabling highly specific and efficient silencing of proteins involved in disease pathogenesis. Despite nearly 20 years of research dedicated to translating siRNA from a research tool into a clinically relevant therapeutic, minimal success has been had to date. Access to RNA interference machinery located in the cytoplasm is often overlooked, but must be considered when designing the next generation of siRNA delivery strategies. Peptide transduction domains (PTDs) have demonstrated moderate siRNA transfection, which is primarily limited by endosomal entrapment. Strategies aimed at overcoming endosomal entrapment associated with peptide vectors are reviewed here, including osmotic methods, lipid conjugation, and fusogenic peptides. As an alternative to traditional PTD, the hemolytic peptide melittin exhibits the native capacity for endosomal disruption but causes cytotoxicity. However, appropriate packaging and protection of melittin with activation and release in the endosomal compartment has allowed melittin-based strategies to demonstrate both in vitro and in vivo safety and efficacy. These data suggest that melittin's membrane disruptive properties can enable safe and effective endosomolysis, building a case for melittin as a key component in a new generation of siRNA therapeutics.

Indexed as

EndosomesMelittenRNA InterferenceRNA, Small InterferingTransfectionMelittenRNA, Small InterferingEndosomal escapeMelittinsiRNA delivery

Identifiers

PMID26025036
PMCPMC4540690
OpenAlexW360531499

What OpenQuestion holds

Textmetadata
LicenceTDM
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.