Evidence map›Paper›PMID 40550952›Full record

ArticlePharmaceutical research2025

Efficient Cytosolic Delivery of siRNA Using Lyophilized and Reconstituted Polymer-siRNA Polyplexes.

Harini Nagaraj, Taewon Jeon, Yagiz Anil Cicek, Ritabrita Goswami, Nourina Nasim, Rukmini Mhaske, Vincent M Rotello

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Article in Pharmaceutical research, 2025. 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. 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

7 authors.

Harini Nagaraj *Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA, 01003, USA.
Taewon Jeon *Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, 230 Stockbridge Road, Amherst, MA, 01003, USA.
Yagiz Anil CicekDepartment of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA, 01003, USA.
Ritabrita GoswamiDepartment of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA, 01003, USA.
Nourina NasimDepartment of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA, 01003, USA.
Rukmini MhaskeDepartment of Biochemistry and Molecular Biology, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA, 01003, USA.
Vincent M RotelloDepartment of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA, 01003, USA. rotello@chem.umass.edu.ORCID http://orcid.org/0000-0002-5184-5439

Funding

NIBIB NIH HHS EB02264
6 · The paper itself

Abstract

purposesiRNA enables highly specific and targeted gene silencing, offering potential treatment for a range of diseases. Cytosolic access of siRNA is essential for efficacy; Current delivery systems generally use endosomal uptake pathways, leading to siRNA degradation due to inefficient escape. Guanidinium functionalized poly(oxanorbornene)imide (PONI) polymers facilitate direct cytosolic siRNA delivery with excellent gene knockdown efficacy in vitro and in vivo. The use of lyophilization to generate stable powders that retain excellent delivery and knockdown activity when reconstituted is demonstrated, providing a key tool for translation.

methodsPONI-Guan polymers were mixed with siRNA to form PONI-Guan/siRNA polyplexes. The generated polyplexes were lyophilized and stored at varying temperature conditions for a total duration of 4 weeks. After reconstitution and delivery, cytosolic access of siRNA was assessed through confocal laser scanning microscopy. Knockdown efficacy was assessed in GFP expressing reporter deGFP HEK 293 T cell line using flow cytometry. Efficacy of reconstituted PONI-Guan/si_STAT3 in 4T1 breast cancer cells was evaluated by quantifying gene expression levels (qRT-PCR) and cell growth inhibition (Alamar blue assay). Delivery and therapeutic efficiency were compared between lyophilized and freshly made polyplexes.

resultsLyophilized polyplexes retained critical functional features of freshly made polyplexes. Resuspended polyplexes facilitated effective cytosolic delivery siRNA and showed therapeutic relevance through the delivery of siRNA targeting STAT-3 gene in 4T1 cells with successful cell growth inhibition (~ 70%) and knockdown (~ 80%) of the gene.

conclusionOverall, this strategy signifies a highly transferrable and versatile method for effective storage of siRNA.

Indexed as

CytosolPolymersRNA, Small InterferingAnimalsCell Line, TumorFreeze DryingGene Knockdown TechniquesGene SilencingGuanidineHEK293 CellsHumansImidazolesMiceSTAT3 Transcription FactorGuanidineImidazolesPolymersRNA, Small InterferingSTAT3 protein, humanSTAT3 Transcription FactorlyophilizationpolymerspolyplexsiRNA

Identifiers

PMID40550952

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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.