Evidence map›Paper›PMID 34091054›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021

Highly efficient CD4+ T cell targeting and genetic recombination using engineered CD4+ cell-homing mRNA-LNPs.

István Tombácz, Dorottya Laczkó, Hamna Shahnawaz, Hiromi Muramatsu, Ambika Natesan, Amir Yadegari, Tyler E Papp, Mohamad-Gabriel Alameh, Vladimir Shuvaev, Barbara L Mui and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 176 papers.

0numbers the graph read from it
0cells of the map it votes in
176citing papers in PubMed
11.5field-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

176 citing papers in PubMed, 254 citations in OpenAlex.

  1. Article
  2. Review
  3. Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026
    Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Nanomaterials Drive In Vivo CAR Immune Cells Engineering.Advanced materials (Deerfield Beach, Fla.) · 2026
    Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. DNA-directed assembly of multivalent lipid nanoparticles for targeted T cell gene delivery.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Article
  17. Article
  18. Review
  19. 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
  20. Review

116 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

15 authors at 2 institutions in 2 countries.

István TombáczDivision of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Dorottya LaczkóDivision of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Hamna ShahnawazDivision of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Hiromi MuramatsuDivision of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ambika NatesanDivision of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Amir YadegariDivision of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Tyler E PappDivision of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mohamad-Gabriel AlamehDivision of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Vladimir ShuvaevDepartment of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Barbara L MuiAcuitas Therapeutics, Vancouver, BC V6T 1Z3, Canada.
Ying K TamAcuitas Therapeutics, Vancouver, BC V6T 1Z3, Canada.
Vladimir MuzykantovDepartment of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Norbert PardiDivision of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Drew WeissmanDivision of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: dreww@pennmedicine.upenn.edu.
Hamideh ParhizDivision of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: Hamideh.Parhiz@pennmedicine.upenn.edu.
University of Pennsylvania · USAcuitas Therapeutics (Canada) · CA

Funding

Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Ronald G Collman · 1999 to 2026
$78.6M
Nucleoside modified mRNA based HIV vaccineR01AI124429 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WEISSMAN, DREW · 2016 to 2019
$3.4M
In Vivo RNA-Mediated Gene Editing of Hemophilia AR01HL134839 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI WEISSMAN, DREW · 2017 to 2020
$2.8M
NHLBI NIH HHS R01 HL134839NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI124429
6 · The paper itself

Abstract

Nucleoside-modified messenger RNA (mRNA)-lipid nanoparticles (LNPs) are the basis for the first two EUA (Emergency Use Authorization) COVID-19 vaccines. The use of nucleoside-modified mRNA as a pharmacological agent opens immense opportunities for therapeutic, prophylactic and diagnostic molecular interventions. In particular, mRNA-based drugs may specifically modulate immune cells, such as T lymphocytes, for immunotherapy of oncologic, infectious and other conditions. The key challenge, however, is that T cells are notoriously resistant to transfection by exogenous mRNA. Here, we report that conjugating CD4 antibody to LNPs enables specific targeting and mRNA interventions to CD4+ cells, including T cells. After systemic injection in mice, CD4-targeted radiolabeled mRNA-LNPs accumulated in spleen, providing ∼30-fold higher signal of reporter mRNA in T cells isolated from spleen as compared with non-targeted mRNA-LNPs. Intravenous injection of CD4-targeted LNPs loaded with Cre recombinase-encoding mRNA provided specific dose-dependent loxP-mediated genetic recombination, resulting in reporter gene expression in about 60% and 40% of CD4+ T cells in spleen and lymph nodes, respectively. T cell phenotyping showed uniform transfection of T cell subpopulations, with no variability in uptake of CD4-targeted mRNA-LNPs in naive, central memory, and effector cells. The specific and efficient targeting and transfection of mRNA to T cells established in this study provides a platform technology for immunotherapy of devastating conditions and HIV cure.

Indexed as

AnimalsCD4-Positive T-LymphocytesCOVID-19COVID-19 VaccinesHumansImmunotherapyLipidsLymph NodesMiceMice, Inbred C57BLNanoparticlesRecombination, GeneticRNA, MessengerSARS-CoV-2SpleenTransfectionCOVID-19 VaccinesLipidsRNA, Messengergenetic recombinationlipid nanoparticleLNPmRNAtargeted mRNA deliveryT cell

Identifiers

PMID34091054
PMCPMC8571164
OpenAlexW3166016270

What Socratic 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 Socratic graph.