Evidence map›Paper›PMID 40650657›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Divergent Delivery and Expression Kinetics of Lipid and Polymeric Nanoparticles across mRNA Modalities.

Irafasha C Casmil, Josh J Friesen, Nuthan V Bathula, Anneke Strumpel, Chia Hao Ho, Ilana Guez, Kristen Y S Kong, Andrew J Varley, Shigeki J Miyake-Stoner, Parinaz Aliahmad and 3 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Enhanced efficacy of a next-generation EEEV self-replicating RNA platform for combination cancer immunotherapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  5. Frontiers in immunology · 2026
    Review
  6. 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

13 authors.

Irafasha C CasmilMichael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, Canada.
Josh J FriesenMichael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, Canada.
Nuthan V BathulaMichael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, Canada.
Anneke StrumpelMichael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, Canada.
Chia Hao HoMichael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, Canada.
Ilana GuezMichael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, Canada.
Kristen Y S KongMichael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, Canada.
Andrew J VarleyMichael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, Canada.
Shigeki J Miyake-StonerReplicate Bioscience Inc, San Diego, CA, 92121, USA.
Parinaz AliahmadReplicate Bioscience Inc, San Diego, CA, 92121, USA.
Nathaniel S WangReplicate Bioscience Inc, San Diego, CA, 92121, USA.
Andrew J GeallReplicate Bioscience Inc, San Diego, CA, 92121, USA.
Anna K BlakneyMichael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, Canada.ORCID https://orcid.org/0000-0002-5812-9689

Funding

CIHRNatural Sciences and Engineering Research Council of CanadaReplicate Biosciences Inc.
6 · The paper itself

Abstract

Messenger ribonucleic acid (mRNA)-based therapies, including conventional linear mRNA (linRNA), circular RNA (circRNA), and self-amplifying RNA (saRNA), are being developed not only for vaccination but also for protein replacement, gene editing, and regenerative medicine. However, these mRNA modalities differ in structure and function, and their interactions with current non-viral delivery systems influence their therapeutic efficacy. Here, the in vivo expression kinetics of linRNA, circRNA, and saRNA delivered via lipid nanoparticles (LNPs) or bioreducible poly(cystamine bisacrylamide-co-4-amino-1-butanol) (pABOL) polymer are systematically evaluated. At 0.5 µg, Venezuelan equine encephalitis virus (VEEV)-based saRNA resulted in higher total luciferase expression than 5 µg of linRNA or circRNA highlighting its superior potency. LNPs significantly enhanced expression of non-amplifying mRNAs compared to pABOL, whereas pABOL delivery of saRNA yielded a ∼2-fold improvement over LNPs. Furthermore, saRNAs derived from New World alphaviruses expressed 2-6 times more protein than Old World saRNAs when delivered with LNPs; these differences are not observed with pABOL. These findings demonstrate that mRNA modality, saRNA genotype, and delivery platform interact to determine therapeutic protein output. This study provides actionable insights for optimizing mRNA-based therapeutics across diverse clinical applications.

Indexed as

Nanoparticle Drug Delivery SystemNanoparticlesRNA, MessengerAnimalsFemaleInjections, IntramuscularMiceMice, Inbred BALB CmRNA VaccinesmRNA VaccinesNanoparticle Drug Delivery SystemRNA, Messengercircular mRNAexpressionlinear mRNAlipid nanoparticlespABOLself‐amplifying mRNA

Identifiers

PMID40650657
PMCPMC12520532

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.