ArticleJACS Au2022
Combinatorial Polycation Synthesis and Causal Machine Learning Reveal Divergent Polymer Design Rules for Effective pDNA and Ribonucleoprotein Delivery.
Article in JACS Au, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
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.
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Who cites it
28 citing papers in PubMed, 62 citations in OpenAlex.
- Modeling lung adenocarcinoma using layer-by-layer nanoparticles mitigates innate immune cell activation.bioRxiv : the preprint server for biology · 2026Article
- Potentials of Machine Learning in Predicting Key Features of Synthetic Antimicrobial Polymers.ACS polymers Au · 2026Article
- Gene Delivery Mediated by Backbone-Degradable RAFT Copolymers.Biomacromolecules · 2026Article
- Poly(beta-amino esters): applications in immunology.Chemical science · 2026Review
- Computational design of functional random heteropolymers through atomistic simulations.PloS one · 2026Article
- Payload-Driven Design of Polymeric Carriers for Nucleic Acid Delivery: Insights from Structure-Function Relationships.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- High-Efficiency l‑PEI-Based Transfection of ARPE-19 Cells Using a Multiparametric Approach and Automated Polyplex Formation with a 3D-Printed Microfluidic System.Chem & bio engineering · 2025Article
- From Bits to Bonds: High-Throughput Virtual Screening of Ribonucleic Acid Nanocarriers Using a Combinatorial Approach of Machine Learning and Molecular Dynamics.Journal of the American Chemical Society · 2025Article
- Seeking Precise Protein-like Functions from Random Heteropolymer Ensemble and through Dimensionality Reduction.ACS central science · 2025Review
- Advancing engineering design strategies for targeted cancer nanomedicine.Nature reviews. Cancer · 2025Review
- Tuning DLVO Interactions Alters Polymer-Mediated pDNA Delivery in a Cell Type-Dependent Manner.Langmuir : the ACS journal of surfaces and colloids · 2025Article
- The Spatial Distribution of Lipophilic Cations in Gradient Copolymers Regulates Polymer-pDNA Complexation, Polyplex Aggregation, and Intracellular pDNA Delivery.Biomacromolecules · 2024Article
- Mapping Biomaterial Complexity by Machine Learning.Tissue engineering. Part A · 2024Review
- Beyond Lipids: Exploring Advances in Polymeric Gene Delivery in the Lipid Nanoparticles Era.Advanced materials (Deerfield Beach, Fla.) · 2024Review
- Poly(l-glutamic acid) augments the transfection performance of lipophilic polycations by overcoming tradeoffs among cytotoxicity, pDNA delivery efficiency, and serum stability.RSC applied polymers · 2024Article
- Polymer designChemical science · 2024Article
- Poly(β-aminoester) Physicochemical Properties Govern the Delivery of siRNA from Electrostatically Assembled Coatings.Biomacromolecules · 2024Article
- Dynamic carriers for therapeutic RNA delivery.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Machine learning coupled with causal inference to identify COVID-19 related chemicals that pose a high concern to drinking water.iScience · 2024Article
- Applied machine learning as a driver for polymeric biomaterials design.Nature communications · 2023Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of polymers that can replace engineered viral vectors in clinical gene therapy has proven elusive despite the vast portfolios of multifunctional polymers generated by advances in polymer synthesis. Functional delivery of payloads such as plasmids (pDNA) and ribonucleoproteins (RNP) to various cellular populations and tissue types requires design precision. Herein, we systematically screen a combinatorially designed library of 43 well-defined polymers, ultimately identifying a lead polycationic vehicle (P38) for efficient pDNA delivery. Further, we demonstrate the versatility of P38 in codelivering spCas9 RNP and pDNA payloads to mediate homology-directed repair as well as in facilitating efficient pDNA delivery in ARPE-19 cells. P38 achieves nuclear import of pDNA and eludes lysosomal processing far more effectively than a structural analogue that does not deliver pDNA as efficiently. To reveal the physicochemical drivers of P38's gene delivery performance, SHapley Additive exPlanations (SHAP) are computed for nine polyplex features, and a causal model is applied to evaluate the average treatment effect of the most important features selected by SHAP. Our machine learning interpretability and causal inference approach derives structure-function relationships underlying delivery efficiency, polyplex uptake, and cellular viability and probes the overlap in polymer design criteria between RNP and pDNA payloads. Together, combinatorial polymer synthesis, parallelized biological screening, and machine learning establish that pDNA delivery demands careful tuning of polycation protonation equilibria while RNP payloads are delivered most efficaciously by polymers that deprotonate cooperatively
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Registered trials
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.