Evidence map›Paper›PMID 41203968›Full record

ArticleNature nanotechnology2025

Degradable cyclic amino alcohol ionizable lipids as vectors for potent influenza mRNA vaccines.

Arnab Rudra, Akash Gupta, Kaelan Reed, Amy Deik, Jiyeon Min, Hasan Mansour A Mansour, Quang Trung Chinh Nguyen, Austin Danko, Yizong Hu, Allegra Berger and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature nanotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Nanomaterials-Based Immunotherapy for Atherosclerosis.Small (Weinheim an der Bergstrasse, Germany) · 2026
    Review
  2. Article
  3. Article
  4. 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

16 authors.

Arnab Rudra *Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1704-5534
Akash Gupta *David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-5614-2313
Kaelan Reed *David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0082-1613
Amy DeikBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-9687-0953
Jiyeon MinBiophysics Program, Institute for Physical Science and Technology, University of Maryland, College Park, MD, USA.ORCID http://orcid.org/0009-0006-8086-095X
Hasan Mansour A MansourDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-1422-5062
Quang Trung Chinh NguyenDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0009-0006-6007-1988
Austin DankoDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Yizong HuDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Allegra BergerDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Michaela PradoDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-1024-7176
Amira BeckDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Clary B ClishBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Jeffery B KlaudaBiophysics Program, Institute for Physical Science and Technology, University of Maryland, College Park, MD, USA.ORCID http://orcid.org/0000-0001-8725-1870
Robert LangerDepartment of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4255-0492
Daniel G AndersonDepartment of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA. dgander@mit.edu.ORCID http://orcid.org/0000-0001-5629-4798

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
Combinatorial and computational design of bnAb mRNA vaccines for HIVR61AI161805 · NIAID · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ANDERSON, DANIEL G · 2021 to 2023
$2.1M
NCI NIH HHS P30 CA014051NIAID NIH HHS R61 AI161805U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 5P30-CA014051U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R61AI161805
6 · The paper itself

Abstract

The next generation of mRNA vaccines must address several limitations, including enhancing vaccine potency and reducing toxicity. Here we develop a class of degradable, cyclic amino ionizable lipids via sequential combinatorial chemistry and rational design. Lipid nanoparticles (LNPs) formulated with the top-performing ionizable lipid, AMG1541, elicited similar protective neutralization antibody titres against an H3 influenza antigen when compared with the FDA-approved ionizable lipid SM-102 at a 100-fold lower dose, with enhanced clearance in vivo. AMG1541 mRNA LNPs substantially reduced expression in the liver following intramuscular injection, mitigating the associated toxicity. We also observed improved mRNA delivery to antigen-presenting cells at the injection site and the draining lymph node, leading to stronger germinal centre reactions. Structure-activity relationship studies suggest that cyclic headgroups and β-amino alcohols facilitate interactions with the mRNA backbone and enhance endosomal escape. The formulations developed here significantly enhance the potency of mRNA vaccines, and our structural insights may guide the development of next-generation vaccine delivery systems.

Indexed as

Amino AlcoholsInfluenza VaccinesLipidsRNA, MessengerAnimalsFemaleHumansLiposomesMiceMice, Inbred BALB CmRNA VaccinesNanoparticlesAmino AlcoholsInfluenza VaccinesLipid NanoparticlesLipidsLiposomesmRNA VaccinesRNA, Messenger

Identifiers

PMID41203968
PMCPMC13387048

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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.