Pharmaceutics2026ResearchNon-viral Gene DeliveryDrug Delivery
Teng Y, Xu X, Gao J, Liu J
Background : Infantile hemangioma (IH) is the most common benign vascular tumor of infancy, and propranolol, the current first-line treatment, requires prolonged twice-daily dosing and has adverse systemic effects. Methods : Using the public GSE127487 transcriptomic dataset together with weighted gene coexpression…
Read the article →Nature Communications2023ResearchNon-viral Gene Delivery
Yue Wang, Shi-Kun Zhou, Yan Wang, Zi-Dong Lu, Yue Zhang, Cong-Fei Xu, Jun Wang
PD-1/PD-L1 blockade therapy is successful but often yields poor benefits due to insufficient T-cell infiltration and low intratumoral concentrations of PD-1/PD-L1 inhibitors. While strategies exist to increase either T-cell recruitment or inhibitor delivery, none actively recruit T cells while achieving…
Read the article →International Journal of Nanomedicine2023ResearchNon-viral Gene Delivery
Hannah J Vaughan, Camila G Zamboni, Kathryn M Luly, Ling Li, Kathleen L Gabrielson, Laboni F Hassan, Nicholas P Radant, Pranshu Bhardwaj, Florin M Selaru, Martin G Pomper, Jordan J Green
Hepatocellular carcinoma (HCC) has limited treatment options, with modest survival after systemic chemotherapy or transarterial chemoembolization (TACE). Gene therapies hold promise for treating HCC, but delivery remains a critical hurdle. While poly(beta-amino ester) (PBAE) nanoparticles have shown efficacy in…
Read the article →Journal of Controlled Release 344 (2022ResearchNon-viral Gene Delivery
Hamideh Parhiz, Jacob S. Brenner, Priyal N. Patel, Tyler E. Papp, Hamna Shahnawaz, Qin Li, Ruiqi Shi, Marco E. Zamora, Amir Yadegari, Oscar A. Marcos-Contreras, Ambika Natesan, Norbert Pardi, Vladimir V. Shuvaev, Raisa Kiseleva, Jacob W. Myerson, Thomas Uhler, Rachel S. Riley, Xuexiang Han, Michael
Nucleoside-modified mRNA lipid nanoparticle (modmRNA-LNP) technology is clinically successful, but its behaviour in pre-existing inflammatory or immune-challenged conditions is poorly characterised. This gap raises the risk of adverse effects when modmRNA-LNPs are administered to patients with ongoing inflammation…
Read the article →Journal of Controlled Release 341 (2022ResearchNon-viral Gene Delivery
Kelsey L. Swingle, Margaret M. Billingsley, Sourav K. Bose, Brandon White, Rohan Palanki, Apeksha Dave, Savan K. Patel, Ningqiang Gong, Alex G. Hamilton, Mohamad-Gabriel Alameh, Drew Weissman, William H. Peranteau, Michael J. Mitchell
Congenital protein deficiencies often begin irreversible pathology in utero, but postnatal treatments are limited. In utero mRNA delivery could enable protein replacement before disease onset, yet LNP stability in fetal amniotic fluid and how it affects mRNA delivery had not been previously investigated. LNP A12 was…
Read the article →Journal of Controlled Release2022ResearchNon-viral Gene Delivery
Martijn J.W. Evers, Wenjuan Du, Qiangbing Yang, Sander A.A. Kooijmans, Aryan Vink, Mies Van Steenbergen, Pieter Vader, Saskia C.A. De Jager, Sabine A. Fuchs, Enrico Mastrobattista, Joost P.G. Sluijter, Zhiyong Lei, Raymond Schiffelers
Modified mRNA (modRNA) is a promising cardiac regeneration therapeutic, but naked mRNA is large, negatively charged, and rapidly degraded. It is unknown whether systemically administered lipid nanoparticles (LNPs) can functionally deliver mRNA to ischaemic/damaged myocardium after myocardial infarction. LNPs were…
Read the article →Chemistry and Physics of Lipids 243 (2022ResearchNon-viral Gene Delivery
Yihua Pei, Yanjie Bao, Cristiano Sacchetti, Juthamart Brady, Kyra Gillard, Hailong Yu, Scott Roberts, Kumar Rajappan, Steven P. Tanis, Carlos G. Perez-Garcia, Padmanabh Chivukula, Priya P. Karmali
Systemic LNP delivery predominantly targets the liver, while extrahepatic delivery—especially to lung airway epithelium for diseases such as cystic fibrosis—remains challenging. DOTAP is a common cationic lipid for lung gene delivery but is racemic, pseudo-glyceryl, and slowly biodegradable. Novel readily…
Read the article →Frontiers in Pharmacology2022ResearchNon-viral Gene Delivery
Sajid Iqbal, Alessandro Francisco Martins, Muhammad Sohail, Jingjing Zhao, Qi Deng, Muhan Li, Zhongxi Zhao
Polymeric gene delivery vectors require detailed physicochemical characterisation to ensure reproducible formulation and efficient transfection. PBAE-447 is a promising biodegradable cationic polymer, but its simple nanoparticles can degrade or aggregate in aqueous/physiological conditions. This study characterises…
Read the article →Nature Biomedical Engineering2021ResearchNon-viral Gene Delivery
Ian C. Miller, Ali Zamat, Lee-Kai Sun, Hathaichanok Phuengkham, Adrian M. Harris, Lena Gamboa, Jason Yang, John P. Murad, Saul J. Priceman, Gabriel A. Kwong
CAR T cell therapy for solid malignancies typically results in poor responses. Systemic administration of immunomodulatory biologics (cytokines, BiTEs) can augment T cell activity but off-target toxicity narrows the therapeutic window. A method to spatially and temporally control transgene expression by engineered T…
Read the article →Biotechnology and Bioengineering (accepted manuscript)2021ResearchNon-viral Gene Delivery
Emily Harris, Devon Zimmerman, Eric Warga, Anil Bamezai, Jacob Elmer
Retroviral gene delivery for T cell therapies is expensive, semi-randomly integrating, and variable between patients. Non-viral alternatives are needed, but T cells are notoriously hard to transfect, especially primary T cells. Lipofectamine LTX was the best vehicle in Jurkat cells; optimised conditions in X-VIVO…
Read the article →Nano Letters2021ResearchNon-viral Gene Delivery
Sarah J. Shepherd, Claude C. Warzecha, Sagar Yadavali, Rakan El-Mayta, Mohamad-Gabriel Alameh, Lili Wang, Drew Weissman, James M. Wilson, David Issadore, Michael J. Mitchell
Microfluidic mixing can produce precise LNPs but is limited in throughput, while bulk mixing is scalable but yields larger, heterogeneous particles with variable potency. A scalable microfluidic device is needed to produce potent RNA-LNPs across discovery and clinical scales. PMD achieved 18.4 L/h production…
Read the article →International Journal of Polymeric Materials and Polymeric Biomaterials2021ResearchNon-viral Gene Delivery
Liu T, Lin M, Wu F, Lin A, Luo D, Zhang Z
siRNA therapeutics are limited by poor cellular uptake, serum nuclease degradation, and inefficient endosomal/lysosomal escape. Chitosan is biocompatible and biodegradable but has low transfection efficiency, largely due to poor buffering capacity and weak endosomal escape. Histidine grafting was explored to add…
Read the article →Materials Science and Engineering: C2021ResearchDrug Delivery
Jiayu Zhou, Yishu Zhai, Jumei Xu, Tian Zhou, Lian Cen
PLGA microspheres are widely used for controlled drug release, but they often exhibit pronounced initial or mid-term burst release. A strategy is needed to finely tune drug release kinetics and suppress burst release, especially for water-soluble drugs. MSNs: Average size 119 nm; specific surface area 902.53 m²/g…
Read the article →Applied Materials Today2020ResearchNon-viral Gene Delivery
Jing Zhao, Danping Lu, Sergio Moya, Haoying Yan, Miaojuan Qiu, Junzong Chen, Xincheng Wang, Yang Li, Haobo Pan, Guochuang Chen, Guocheng Wang
Bispecific T-cell engager (BiTE) immunotherapy is a promising cancer treatment, but clinical application is limited by high production costs and short in vivo half-life of BiTE proteins. A gene delivery system that enables sustained in vivo expression of BiTE could overcome these limitations, but existing non-viral…
Read the article →Nature Communications2020ResearchNon-viral Gene Delivery
John C. Charpentier, Di Chen, Philip E. Lapinski, Jackson Turner, Irina Grigorova, Joel A. Swanson, Philip D. King
Macropinocytosis has been shown to regulate the growth of Ras-transformed tumour cells under amino acid (AA)-limiting conditions by providing extracellular proteins that are degraded into AA to fuel cell growth and activate mTORC1. However, whether macropinocytosis regulates the growth of non-transformed mammalian…
Read the article →Cancers (MDPI)2020ResearchNon-viral Gene Delivery
Julie J.-J. Tang, Alina P. Sung, Mariel J. Guglielmo, Laura N.-G., Doug Redelman, James Smith-Gagen, Diane Hudig
Monoclonal antibody anti-tumour therapies rely on NK cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC), but patient responses vary widely. While tumour antigen escape is one cause of treatment failure, the role of inter-individual variation in NK cell serial killing capacity—the ability of a single…
Read the article →Cancer Immunology Research (AACR)2020ResearchNon-viral Gene Delivery
Dylan J. Drakes, Sarwish Rafiq, Terence J. Purdon, Andrea V. Lopez, Smita S. Chandran, Christopher A. Klebanoff, Renier J. Brentjens
T-cell receptor (TCR)-modified T-cell gene therapy can target a variety of extracellular and intracellular tumour-associated antigens, yet has had little clinical success. A potential explanation for limited antitumor efficacy is a lack of T-cell activation in vivo, particularly when tumour cells downregulate…
Read the article →Journal of Controlled Release2020ResearchNon-viral Gene Delivery
Pedro P. Guimaraes, Rui Zhang, Roman Spektor, Mingchee Tan, Amanda Chung, Margaret M. Billingsley, Rakan El-Mayta, Rachel S. Riley, Lili Wang, James M. Wilson, Michael J. Mitchell
LNP libraries are usually screened in vitro, which poorly predicts in vivo mRNA delivery. A high-throughput in vivo platform was needed to screen many LNP formulations simultaneously and identify lead carriers for functional mRNA delivery. b-mRNA could be detected in liver at doses as low as 17 ng; b-mRNA delivery…
Read the article →Science Advances2020ResearchNon-viral Gene Delivery
Elana Ben-Akiva, Randall A. Meyer, Hongzhe Yu, Jonathan T. Smith, Drew M. Pardoll, Jordan J. Green
Previous red blood cell (RBC) membrane-coated nanoparticles have all been spherical, missing the physical shape component of biomimicry. Particle shape is a critical design parameter affecting biodistribution, macrophage evasion, and targeted interactions. A platform combining physical biomimicry (anisotropic shape)…
Read the article →Journal of Materials Chemistry B2020ResearchNon-viral Gene Delivery
Yana Tarakanchikova, Albert Muslimov, Igor Sergeev, Kirill Lepik, Nikita Yolshin, Alexander Goncharenko, Kirill Vasilyev, Igor Eliseev, Anton Bukatin, Vladislav Sergeev, Sergey Pavlov, Alexey Popov, Igor Meglinski, Boris Afanasyev, Bogdan Parakhonskiy, Gleb Sukhorukov, Dmitry Gorin
DNA- and mRNA-based therapies are transforming biomedicine, but intracellular delivery—especially to hard-to-transfect, clinically relevant cells such as primary human T lymphocytes—remains a major barrier. Existing non-viral methods often suffer from low transfection efficiency, high toxicity, or complex…
Read the article →Biophysical Journal2019ResearchNon-viral Gene Delivery
Janusz Khetan, Madhan Srikar, Daniel B. Forger, Sutapa Barua
The general perception is that cellular uptake of materials is proportional to cell volume (mass) or surface area, following cubic or square relationships with cell radius. However, experimental data on nanoparticle uptake in MDA-MB 231 breast cancer cells show a linear relationship with cell radius—a result that is…
Read the article →Nature2019ResearchNon-viral Gene Delivery
Haig Aghajanian, Toru Kimura, Joel G. Rurik, Aidan S. Hancock, Michael S. Leibowitz, Li Li, John Scholler, James Monslow, Albert Lo, Wei Han, Tao Wang, Kenneth Bedi, Michael P. Morley, Ricardo A. Linares Saldana, Nikhita A. Bolar, Kendra Mcdaid, Charles-Antoine Assenmacher, Cheryl L. Smith, Dagmar W
Fibrosis is observed in nearly every form of myocardial disease and contributes to heart failure, yet clinical interventions targeting fibrosis remain limited. No therapies directly target excessive cardiac fibrosis, and very few interventions improve cardiac function in patients with impaired compliance. Genetic…
Read the article →Nanoscale2019ResearchNon-viral Gene Delivery
Dongyu Chen, Neha Parayath, Shanthi Ganesh, Weimin Wang, Mansoor Amiji
The protein corona that forms on lipid nanoparticles (LNPs) after systemic administration can alter their biological identity, but its impact on tumour delivery is not well understood. This study aimed to determine whether LNP formulation composition and surface charge can manipulate the protein corona and thereby…
Read the article →Journal of Controlled Release2019ResearchNon-viral Gene Delivery
Yusuke Sato, Kazuki Hashiba, Kosuke Sasaki, Masatoshi Maeki, Manabu Tokeshi, Hideyoshi Harashima
Endosomal escape remains a major rate-limiting step for siRNA delivery. The structure–activity relationships (SAR) of pH-sensitive cationic lipids were incompletely understood, limiting rational design of lipid nanoparticles (LNPs) for efficient in vivo siRNA delivery to hepatocytes. Hydrophilic head group structure…
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