Evidence map›Paper›PMID 29891683›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

Enhanced mRNA delivery into lymphocytes enabled by lipid-varied libraries of charge-altering releasable transporters.

Colin J McKinlay, Nancy L Benner, Ole A Haabeth, Robert M Waymouth, Paul A Wender

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed
8.4field-weighted citation impact, top 2% 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

111 citing papers in PubMed, 237 citations in OpenAlex.

  1. Article
  2. Review
  3. Reprogramming CD22 CAR-T cells in vivo using CD8-targeted mRNA-LNPs to treat hematological malignancies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Journal of the American Chemical Society · 2025
    Article
  9. Review
  10. Article
  11. Article
  12. Functional Polyesters: Tailoring Structure and Biomedical Functions.Polymer science & technology (Washington, D.C.) · 2025
    Review
  13. Review
  14. Article
  15. Review
  16. Unlocking Transplant Tolerance with Biomaterials.Advanced healthcare materials · 2025
    Review
  17. Review
  18. Review
  19. Review
  20. Review

51 more citing papers are in PubMed but not listed here.

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

5 authors at 1 institution in 1 country.

Colin J McKinlayDepartment of Chemistry, Stanford University, Stanford, CA 94305.
Nancy L BennerDepartment of Chemistry, Stanford University, Stanford, CA 94305.
Ole A HaabethDivision of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, CA 94305.
Robert M WaymouthDepartment of Chemistry, Stanford University, Stanford, CA 94305; waymouth@stanford.edu wenderp@stanford.edu.
Paul A WenderDepartment of Chemistry, Stanford University, Stanford, CA 94305; waymouth@stanford.edu wenderp@stanford.edu.
Stanford University · US

Funding

SYNTHETIC STUDIES RELATED TO CANCER RESEARCH/TREATMENTR01CA031845 · NCI · STANFORD UNIVERSITY · PI PAUL Anthony WENDER · 1985 to 2026
$6.9M
SYNTHETIC STUDIES ON TUMOR PROMOTERS AND INHIBITORSR01CA031841 · NCI · STANFORD UNIVERSITY · PI WENDER, PAUL ANTHONY · 1985 to 2014
$4.8M
Synthetic Studies Related to Cancer Research/TreatmentR37CA031845 · NCI · STANFORD UNIVERSITY · PI WENDER, PAUL ANTHONY · 2006 to 2015
$4.5M
BD Canto II RUO CytometerS10RR027431 · NCRR · STANFORD UNIVERSITY · PI NOLAN, GARRY P · 2010 to 2010
$236k
SYNTHETIC STUDIES ON TUMOR PROMOTERS AND INHIBITORSR37CA031841 · NCI · STANFORD UNIVERSITY · PI WENDER, PAUL · 1993 to 1999
–
NCI NIH HHS R01 CA031841NCI NIH HHS R01 CA031845NCI NIH HHS R37 CA031841NCI NIH HHS R37 CA031845NCRR NIH HHS S10 RR027431
6 · The paper itself

Abstract

We report a strategy for generating a combinatorial library of oligonucleotide transporters with varied lipid domains and their use in the efficient transfection of lymphocytes with mRNA in vitro and in vivo. This library is based on amphiphilic charge-altering releasable transporters (CARTs) that contain a lipophilic block functionalized with various side-chain lipids and a polycationic α-amino ester mRNA-binding block that undergoes rearrangement to neutral small molecules, resulting in mRNA release. We show that certain binary mixtures of these lipid-varied CARTs provide up to a ninefold enhancement in mRNA translation in lymphocytes in vitro relative to either a single-lipid CART component alone or the commercial reagent Lipofectamine 2000, corresponding to a striking increase in percent transfection from 9-12% to 80%. Informed by the results with binary mixtures, we further show that CARTs consisting of optimized ratios of the two lead lipids incorporated into a single hybrid-lipid transporter molecule maintain the same delivery efficacy as the noncovalent mixture of two CARTs. The lead lipid CART mixtures and hybrid-lipid CARTs show enhanced lymphocyte transfection in primary T cells and in vivo in mice. This combinatorial approach for rapidly screening mRNA delivery vectors has provided lipid-varied CART mixtures and hybrid-lipid CARTs that exhibit significant improvement in mRNA delivery to lymphocytes, a finding of potentially broad value in research and clinical applications.

Indexed as

Carrier ProteinsGene LibraryLipidsRNA, MessengerAnimalsHumansJurkat CellsLymphocytesMice, Inbred BALB CTransfectionCarrier ProteinsLipidsLipofectamineRNA, Messengercombinatorialgene therapyimmunotherapynanoparticlepolyplex

Identifiers

PMID29891683
PMCPMC6042134
OpenAlexW2808372952

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.