Methods in molecular biology (Clifton, N.J.)2027ResearchNon-viral Gene DeliveryDrug Delivery
Rudolf R, Cesetti T, Keller F, Hafner M
Lipoplex nanoparticle-based vaccination technologies have shown tremendous efficiency for in vivo transfection during the COVID-19 pandemic and also hold promise for treating melanoma. While pharmacodynamics and pharmacokinetics need careful in vivo and clinical testing, other parameters of drug performance can be…
Read the article →Molecular pharmaceutics2026ResearchNon-viral Gene DeliveryDrug Delivery
Kc R, Nasrullah M, Meenakshi Sundaram Dn, Patel D, Sandhu G, Kucharski C, Et Al.
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) has long been identified as a promising therapeutic due to its ability to induce apoptosis selectively in cancer cells. However, poor stability and rapid clearance of the administered TRAIL protein in circulation have hampered its clinical development…
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 →Advanced Science2023ResearchNon-viral Gene Delivery
Cheng Huang, Xing Duan, Jichao Wang, Qingqing Tian, Yangmei Ren, Kepan Chen, Zongliang Zhang, Yuanyou Li, Yunyu Feng, Kunhong Zhong, Yuelong Wang, Liangxue Zhou, Gang Guo, Xiangrong Song, And Aiping Tong
Bispecific T-cell engagers (BiTEs) are promising but require large amounts of purified protein, have high manufacturing costs, poor in vivo stability, and short serum half-lives. mRNA delivery could enable continuous endogenous production of BiTEs, but efficient and safe delivery systems are needed. The study…
Read the article →Nature Communications 14, 345 (2023ResearchNon-viral Gene Delivery
Xuexiang Han, Ningqiang Gong, Lulu Xue, Margaret M. Billingsley, Rakan El-Mayta, Sarah J. Shepherd, Mohamad-Gabriel Alameh, Drew Weissman, Michael J. Mitchell
Liver fibrosis has no approved antifibrotic therapies. Activated hepatic stellate cells (HSCs) drive fibrosis by producing collagen, and HSP47 is a key collagen chaperone in these cells. Targeted delivery of siRNA to activated HSCs remains challenging, so a ligand-tethered LNP platform was developed to deliver RNA…
Read the article →2023ReviewNon-viral Gene Delivery
Pinto Is, Cordeiro Ra, Faneca H
CAR T cell therapy is FDA/EMA-approved for B cell malignancies and multiple myeloma, but manufacturing relies on viral vectors—associated with safety concerns, high cost, and production challenges—or electroporation, which can be highly cytotoxic. Nanosystems may offer a safer, cost-effective alternative, but T cells…
Read the article →Biomaterials Science2022ReviewNon-viral Gene Delivery
Sydney R. Shannon, Elena Ben-Akiva, Jordan J. Green
Gene therapies are transforming treatment for many diseases, but clinical efficacy and safety depend on both the delivery material and the cargo. Non-viral delivery to immune cells remains especially challenging, and no clinical translation breakthrough has yet been achieved for non-viral gene editing. This…
Read the article →Science2022ResearchNon-viral Gene Delivery
Joel G. Rurik, István Tombácz, Amir Yadegari, Pedro O. Méndez Fernández, Swapnil V. Shewale, Li Li, Toru Kimura, Ousamah Younoss Soliman, Tyler E. Papp, Ying K. Tam, Barbara L. Mui, Steven M. Albelda, Ellen Puré, Carl H. June, Haig Aghajanian, Drew Weissman, Hamideh Parhiz, Jonathan A. Epstein
Fibrosis affects millions of people with cardiac disease and contributes to heart failure. While adoptive transfer of CAR T cells targeting fibroblast activation protein (FAP) has shown promise in reducing cardiac fibrosis, conventional CAR T cells persist for months to years and could cause chronic off-target…
Read the article →Accounts of Chemical Research2022ResearchNon-viral Gene Delivery
Yulia Eygieris, Mohit Gupta, Jeonghwan Kim, Gaurav Sahay
LNPs enabled the COVID-19 mRNA vaccines and the first siRNA-LNP drug, but there is still no one-size-fits-all LNP for every RNA therapeutic. A better chemistry-level understanding of LNP self-assembly, component roles, and whole-particle properties is needed to rationally design safer and more efficient RNA delivery…
Read the article →Journal of Controlled Release 349 (2022ResearchNon-viral Gene Delivery
Annabelle Biscans, Socheata Ly, Nicholas Mchugh, David A. Cooper, Anastasia Khvorova
Lipid-conjugated siRNAs can reach extrahepatic tissues, but silencing efficacy remains lower than in liver largely because only ~1–2% of internalised siRNA escapes endosomes into the cytoplasm. Ionisable lipids enhance endosomal escape in lipid nanoparticles (LNPs), but direct covalent conjugation of an ionisable…
Read the article →Journal of Controlled Release 347 (2022ResearchNon-viral Gene Delivery
Savan K. Patel, Margaret M. Billingsley, Caitlin Frazee, Xuexiang Han, Kelsey L. Swingle, Jingya Qin, Mohamad-Gabriel Alameh, Karin Wang, Drew Weissman, Michael J. Mitchell
mRNA delivery to T cells could enable ex vivo and in vivo T cell engineering, but LNPs still face poor extrahepatic delivery, endosomal recycling, and limited T cell transfection. Cholesterol analogs such as hydroxycholesterols may alter NPC1 recognition and endosomal trafficking, providing a route to improve T cell…
Read the article →Biomaterials 281 (2022ResearchNon-viral Gene Delivery
Azadeh Kheirolomoom, Aris J. Kare, Elizabeth S. Ingham, Ramasamy Paulmurugan, Elise R. Robinson, Mo Baikoghli, Mohammed Inayathullah, Jai W. Seo, James Wang, Brett Z. Fite, Bo Wu, Spencer K. Tumble, Marina N. Raie, R. Holland Cheng, Lisa Nichols, Alexander D. Borowsky, Katherine W. Ferrara
Ex vivo T-cell engineering is effective but complex, costly, and difficult to scale. A method to transfect T cells directly in situ could simplify T-cell immunotherapy, but T-cell targeting may also trigger activation, depletion, cytokine release, and phenotypic changes that must be understood. In vitro: 80% of…
Read the article →International Journal of Nanomedicine2022ResearchNon-viral Gene Delivery
Sérgio Scalzo, Anderson K. Santos, Heloisa A. S. Ferreira, Pedro A. Costa, Pedro H. D. M. Prazeres, Natalia J. A. Da Silva, Lays C. Guimarães, Mário De Morais E Silva, Marco T. R. Rodrigues Alves, Celso T. R. Viana, Itamar C. G. Jesus, Alice P. Rodrigues, Alexander Birbrair, Anderson O. Lobo, Freder
Cardiomyocytes are hard-to-transfect cells, and gene therapy for cardiovascular disease is limited by insufficient delivery to cardiac tissue, nucleic acid degradation, and safety concerns with viral vectors. A safe, effective non-viral platform for pDNA delivery to cardiomyocytes is needed. LNP4 was the top…
Read the article →Journal of Biomedical Materials Research Part A2022ResearchNon-viral Gene Delivery
Hanwen Zhang, Xuexiang Han, Mohamad-Gabriel Alameh, Sarah J. Shepherd, Marshall S. Padilla, Lulu Xue, Kamila Butowska, Drew Weissman, Michael J. Mitchell
LNPs can trigger innate immune responses and inflammation, which can suppress mRNA translation and cause adverse effects. There is a need for LNP formulations that reduce LNP-induced inflammation while maintaining or improving mRNA delivery. C9D1 and C10D0 had similar size, PDI, and 90% mRNA encapsulation; Dex…
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 →Journal of Pharmaceutical Investigation.2022ReviewNon-viral Gene Delivery
Karmacharya P, Patil Br, Kim Jo
mRNA is an attractive platform for cancer immunotherapy, but its instability, susceptibility to RNase degradation, and inefficient endosomal escape limit therapeutic applications. Lipid-based nanocarriers are non-viral vectors that can protect mRNA, improve transfection, and deliver it to intracellular compartments…
Read the article →Cancer Gene Therapy* (Springer Nature America, Inc.)2021ReviewNon-viral Gene Delivery
Rakan El-Mayta, Zijing Zhang, Alex G. Hamilton, Michael J. Mitchell
CAR T cell therapies have achieved clinical success but face limitations including restriction to autologous cell sources (to avoid HLA mismatch and GvHD), cumbersome manufacturing, high costs, and poor efficacy in solid tumours. NK cells have emerged as promising alternatives because they can kill cancer cells…
Read the article →Trends in Biotechnology* (as indicated in the article’s Key Figure footer)2021ReviewNon-viral Gene Delivery
Qurrat Ul Ain, Estefania V.R. Campos, Ariel Huynh, Dominik Witzigmann, Sarah Hedtrich
Gene therapies are powerful tools to prevent, treat, and cure human diseases, but their application to skin diseases has received little attention despite the easy accessibility of skin and urgent medical need. The main obstacle is the unique barrier properties of human skin, which severely limit absorption of…
Read the article →Journal of Materials Chemistry B2021ReviewNon-viral Gene Delivery
Rih-Yang Huang, Zhuo-Hao Liu, Wei-Han Weng, Chien-Wen Chang
Gene therapy requires safe, precise, efficient, and cost-effective delivery. Viral vectors are efficient but face manufacturing, cost, and safety challenges; non-viral vectors are safer and more scalable but often have low delivery efficiency. Magnetic nanoparticles (MNPs) have emerged as a promising strategy to…
Read the article →Advanced Materials2021ReviewNon-viral Gene Delivery
Arun R. K. Kumar, Yufeng Shou, Brian Chan, Krishna L., Andy Tay
This review examines how viral vectors, electroporation, microfluidic systems, nanoparticles and high-aspect-ratio nanostructures can improve the efficiency, viability and scalability of transfecting primary immune cells for applications such as CAR-T, CAR-NK and gene editing. It highlights the trade-offs between…
Read the article →Journal of the American Chemical Society (JACS)2021ResearchNon-viral Gene Delivery
Dapeng Zhang, Elena N. Atochina-Vasserman, Devendra S. Maurya, Ning Huang, Qi Xiao, Nathan Ona, Matthew Liu, Hamna Shahnawaz, Houping Ni, Kyunghee Kim, Margaret M. Billingsley, Darrin J. Pochan, Michael J. Mitchell, Drew Weissman, Virgil Percec
Four-component lipid nanoparticles (LNPs) represent the leading non-viral vectors for mRNA delivery, but they have limitations including: (1) segregation of the neutral ionisable lipid as droplets in the LNP core, reducing transfection efficiency to ~1-2%; (2) the "PEG dilemma" where PEGylation increases circulation…
Read the article →Molecular Therapy2021ResearchNon-viral Gene Delivery
Hamideh Parhiz, Jacob S. Brenner, Et Al. (full Author List Not Included In The Supplied Excerpt)
T cells are notoriously resistant to exogenous mRNA transfection, limiting in vivo T cell engineering for immunotherapy, CAR T generation, and HIV cure. A safe, specific, and efficient in vivo mRNA delivery platform for CD4+ T cells was needed. In vitro: anti-CD4/mRNA-LNPs bound specifically to human CD4+ T cells…
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…
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