Evidence map›Paper›PMID 31160223›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019

mRNA Delivery for Therapeutic Anti-HER2 Antibody Expression In Vivo.

Yulia Rybakova, Piotr S Kowalski, Yuxuan Huang, John T Gonzalez, Michael W Heartlein, Frank DeRosa, Derfogail Delcassian, Daniel G Anderson

Open access · hybridAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.

0numbers the graph read from it
0cells of the map it votes in
130citing papers in PubMed
12.3field-weighted citation impact, top 1% 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

130 citing papers in PubMed, 207 citations in OpenAlex.

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  5. Anti-CD19-engineered exosomes enable B cell-targeted anti-BAFF mRNA delivery to alleviate lupus progression.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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70 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

8 authors at 2 institutions in 1 country.

Yulia RybakovaDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Piotr S KowalskiDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Yuxuan HuangDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
John T GonzalezDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Michael W HeartleinTranslate Bio, Lexington, MA 02421, USA.
Frank DeRosaTranslate Bio, Lexington, MA 02421, USA.
Derfogail DelcassianDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Daniel G AndersonDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard and MIT Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: dgander@mit.edu.
Massachusetts Institute of Technology · USTranslate Bio (United States) · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
NCI NIH HHS P30 CA014051
6 · The paper itself

Abstract

Antibody-based drugs are a leading class of biologics used to treat a variety of diseases, including cancer. However, wide antibody implementation is hindered by manufacturing challenges and high production cost. Use of in-vitro-transcribed mRNA (IVT-mRNA) for endogenous protein expression has the potential to circumvent many of the shortcomings of antibody production and therapeutic application. Here, we describe the development of an IVT-mRNA system for in vivo delivery of a humanized anti-HER2 (also known as ERBB2) antibody, trastuzumab, and demonstrate its anticancer activity. We engineered the IVT-mRNA sequence to maximize expression, then formulated the IVT-mRNA into lipid-based nanoparticles (LNPs) to protect the mRNA from degradation and enable efficient in vivo delivery. Systemic delivery of the optimized IVT-mRNA loaded into LNPs resulted in antibody serum concentrations of 45 ± 8.6 μg/mL for 14 days after LNP injection. Further studies demonstrated an improved pharmacokinetic profile of the produced protein compared to injection of trastuzumab protein. Finally, treatment of tumor-bearing mice with trastuzumab IVT-mRNA LNPs selectively reduced the volume of HER2-positive tumors and improved animal survival. Taken together, the results of our study demonstrate that using IVT-mRNA LNPs to express full-size therapeutic antibodies in the liver can provide an effective strategy for cancer treatment and offers an alternative to protein administration.

Indexed as

Gene ExpressionGene Transfer TechniquesAnimalsAntibodies, MonoclonalBreast NeoplasmsDisease Models, AnimalDrug Delivery SystemsErb-b2 Receptor Tyrosine KinasesGenetic TherapyHumansLipidsMiceMolecular Targeted TherapyNanoparticlesRNA, MessengerTrastuzumabAntibodies, MonoclonalERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesLipidsRNA, MessengerTrastuzumabantibody-based drugsbreast cancerHerceptinlipid nanoparticlesmRNA deliverymRNA designmRNA therapeuticstrastuzumab

Identifiers

PMID31160223
PMCPMC6698250
OpenAlexW2945697388

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.