Evidence map›Paper›PMID 39346819›Full record

ArticleACS omega2024

Selective Transfection of a Transferrin Receptor-Expressing Cell Line with DNA-Lipid Nanoparticles.

Irodiel Vinales, Juan Carlos Silva-Espinoza, Bryan A Medina, Juan E M Urbay, Miguel A Beltran, Dante E Salinas, Marco A Ramirez-Ramos, Rosa A Maldonado, Wilson Poon, Manuel L Penichet and 2 more

Abstract read
In one paragraph

Article in ACS omega, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Irodiel VinalesDepartment of Chemistry and Biochemistry, University of Texas at El Paso, El Paso, Texas 79968, United States.ORCID https://orcid.org/0000-0002-4544-9587
Juan Carlos Silva-EspinozaDepartment of Biological Sciences, University of Texas at El Paso, El Paso, Texas 79968, United States.
Bryan A MedinaDepartment of Chemistry and Biochemistry, University of Texas at El Paso, El Paso, Texas 79968, United States.
Juan E M UrbayDepartment of Chemistry and Biochemistry, University of Texas at El Paso, El Paso, Texas 79968, United States.
Miguel A BeltranBorder Biomedical Research Center, University of Texas at El Paso, El Paso, Texas 79968, United States.
Dante E SalinasBorder Biomedical Research Center, University of Texas at El Paso, El Paso, Texas 79968, United States.
Marco A Ramirez-RamosDepartment of Chemistry and Biochemistry, University of Texas at El Paso, El Paso, Texas 79968, United States.
Rosa A MaldonadoBorder Biomedical Research Center, University of Texas at El Paso, El Paso, Texas 79968, United States.ORCID https://orcid.org/0000-0003-3180-7192
Wilson PoonDepartment of Metallurgical, Materials and Biomedical Engineering, University of Texas at El Paso, El Paso, Texas 79968, United States.ORCID https://orcid.org/0000-0003-2192-3077
Manuel L PenichetDivision of Surgical Oncology, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California 90095, United States.
Igor C AlmeidaBorder Biomedical Research Center, University of Texas at El Paso, El Paso, Texas 79968, United States.ORCID https://orcid.org/0000-0002-2443-8213
Katja MichaelDepartment of Chemistry and Biochemistry, University of Texas at El Paso, El Paso, Texas 79968, United States.ORCID https://orcid.org/0000-0001-6754-3702

Funding

UTEP Border Biomedical Research CenterU54MD007592 · NIMHD · UNIVERSITY OF TEXAS EL PASO · PI RENATO J AGUILERA · 2019 to 2026
$35.1M
TOXICOLOGY PROJECTG12RR008124 · NCRR · UNIVERSITY OF TEXAS EL PASO · PI AGUILERA, RENATO J · 1992 to 2011
$20.8M
TCCG12MD007592 · NIMHD · UNIVERSITY OF TEXAS EL PASO · PI KIRKEN, ROBERT A. · 2012 to 2018
$19.4M
A Novel Strategy Targeting TfR1 for the Prevention/Treatment of AIDS-related NHLR01CA196266 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARTINEZ-MAZA, OTONIEL, PENICHET, MANUEL L · 2016 to 2020
$3.4M
A novel gene-based immunotherapy inducing melanoma destructionR21CA283583 · NCI · UNIVERSITY OF TEXAS EL PASO · PI MICHAEL, KATJA · 2024 to 2025
$382k
NCI NIH HHS R01 CA196266NCI NIH HHS R21 CA283583NCRR NIH HHS G12 RR008124NIMHD NIH HHS G12 MD007592NIMHD NIH HHS U54 MD007592
6 · The paper itself

Abstract

Despite considerable progress in using lipid nanoparticle (LNP) vehicles for gene delivery, achieving selective transfection of specific cell types remains a significant challenge, hindering the advancement of new gene or gene-editing therapies. Although LNPs have been equipped with ligands aimed at targeting specific cellular receptors, achieving complete selectivity continues to be elusive. The exact reasons for this limited selectivity are not fully understood, as cell targeting involves a complex interplay of various cellular factors. Assessing how much ligand/receptor binding contributes to selectivity is challenging due to these additional influencing factors. Nonetheless, such data are important for developing new nanocarriers and setting realistic expectations for selectivity. Here, we have quantified the selective, targeted transfection using two uniquely engineered cell lines that eliminate unpredictable and interfering cellular influences. We have compared the targeted transfection of Chinese ovary hamster (CHO) cells engineered to express the human transferrin receptor 1 (hTfR1), CHO-TRVb-hTfR1, with CHO cells that completely lack any transferrin receptor, CHO-TRVb-neo cells (negative control). Thus, the two cell lines differ only in the presence/absence of hTfR1. The transfection was performed with pDNA-encapsulating LNPs equipped with the DT7 peptide ligand that specifically binds to hTfR1 and enables targeted transfection. The LNP's pDNA encoded for the monomeric GreenLantern (mGL) reporter protein, whose fluorescence was used to quantify transfection. We report a novel LNP composition designed to achieve an optimal particle size and ζ-potential, efficient pDNA encapsulation, hTfR1-targeting capability, and sufficient polyethylene glycol sheltering to minimize random cell targeting. The transfection efficiency was quantified in both cell lines separately through flow cytometry based on the expression of the fluorescent gene product. Our results demonstrated an LNP dose-dependent mGL expression, with a 5-fold preference for the CHO-TRVb-hTfR1 when compared to CHO-TRVb-neo. In another experiment, when both cell lines were mixed at a 1:1 ratio, the DT7-decorated LNP achieved a 3-fold higher transfection of the CHO-TRVb-hTfR1 over the CHO-TRVb-neo cells. Based on the low-level transfection of the CHO-TRVb-neo cells in both experiments, our results suggest that 17-25% of the transfection occurred in a nonspecific manner. The observed transfection selectivity for the CHO-TRVb-hTfR1 cells was based entirely on the hTfR1/DT7 interaction. This work showed that the platform of two engineered cell lines which differ only in the hTfR1 can greatly facilitate the development of LNPs with hTfR1-targeting ligands.

Identifiers

PMID39346819
PMCPMC11425831

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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.