Molecular therapy. Nucleic acids2026ResearchNon-viral Gene DeliveryDrug Delivery
Ramamurthy A, Scimonelli G, Murphy Wl, Saha K
Human T cells modified with nucleic acids constitute a powerful and emerging therapeutic modality for cancer, autoimmune disorders, and aging-related diseases. However, delivering nucleic acids, such as mRNA encoding synthetic receptors, transcription factors, cytokines, or genome editors to T cells can be…
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 →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 →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 →Acta Pharmaceutica Sinica B2022ReviewNon-viral Gene Delivery
Yingping Zeng, Sufen Li, Shufen Zhang, Li Wang, Hong Yuan, Fuqiang Hu
Cancer immunotherapy is limited by tumour heterogeneity, immune cell disability, immunosuppressive tumour microenvironment (TME), and systemic immune toxicity. Cell membrane-coated nanoparticles (CMCNs) offer a biomimetic delivery strategy that inherits source-cell functions—immune evasion, tumour targeting, and…
Read the article →Frontiers in Oncology2022ReviewNon-viral Gene Delivery
Tianqing Xin, Li Cheng, Chuchao Zhou, Yimeng Zhao, Zhenhua Hu, Xiaoyan Wu
CAR-T cell therapy has shown impressive success in haematological malignancies, but systemic toxicity (CRS, ICANS, on-target/off-tumour effects) and the complex, costly, individualized manufacturing process of autologous CAR-T cells hinder broader application. Universal allogeneic CAR-T cells have encountered safety…
Read the article →Science Advances2022ReviewNon-viral Gene Delivery
Ann E. Metzloff, Margaret M. Billingsley, Michael J. Mitchell
mRNA vaccines have entered global use, but delivering mRNA to T cells in vivo remains challenging because T cells are non-phagocytic, reside largely in lymphoid tissues, and intravenously administered lipid nanoparticles (LNPs) tend to accumulate in the liver. There is a need for precise, scalable strategies to…
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 →Science Advances2022ResearchNon-viral Gene Delivery
Rasheid Smith, Emad I. Wafa, Sean M. Geary, Kareem Ebeid, Suhaila O. Alhaj-Suliman, Aliasger K. Salem
Cancer vaccines as monotherapies have displayed limited clinical success due to the immunosuppressive tumour microenvironment (TME). Nanoscale formulations can enhance vaccine efficacy by combating TME immunosuppression, but there is a need for novel adjuvant formulations that can be combined with therapeutic cancer…
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 →Signal Transduction and Targeted Therapy2022ReviewNon-viral Gene Delivery
Qin S, Tang X, Chen Y, Et Al.
mRNA therapeutics have fuelled hope to combat incurable diseases, but insufficient understanding of mRNA instability, immunogenicity, and delivery has impeded progress. The review argues that mRNA-based drugs—especially after the COVID-19 vaccine success—can become powerful, versatile tools, and that mRNA…
Read the article →2022ReviewDrug Delivery
Lei W, Yang C, Wu Y, Ru G, He X, Tong X, Wang S.
Conventional chemotherapy suffers from poor targeting and severe side effects, while synthetic nanocarriers are often cleared by the immune system and lack precise tumour targeting. Cell membrane-coated nanocarriers (CMCNs) offer a biomimetic strategy to improve biocompatibility, immune evasion, circulation time, and…
Read the article →2022ReviewNon-viral Gene Delivery
Chuang St, Conklin B, Stein Jb, Pan G, Lee K-B.
Immunotherapy has improved outcomes in cancer and infectious disease, but off-target effects, systemic toxicities, and variable efficacy remain limiting. Nanoscale engineering offers ways to manipulate immune cell functions—enhancing immunity against cancers and pathogens, controlling the site of immune response, and…
Read the article →Materials Today Advances2022ReviewNon-viral Gene Delivery
Randall A. Meyer, Sarah Y. Neshat, Jordan J. Green, Jose Luis Santos, And Anthony D. Tuesca
mRNA gene therapy has broad therapeutic potential (protein replacement, vaccines, regenerative medicine, oncology), but clinical translation is limited by inadequate understanding of how to target specific organs or cell types for protein expression. Reports on material properties and administration routes are…
Read the article →Heart Failure Reviews (Springer)2022ReviewNon-viral Gene Delivery
Paolo Morfino, Alberto Aimo, Vincenzo Castiglione, Carolina Galvez-Montón, Michele Emdin, Antoni Bayes-Genis
Cardiac fibrosis contributes to the pathogenesis of heart failure, myocardial infarction, and arrhythmias, but no primarily anti-fibrotic drug has been approved for cardiovascular disease. Many candidate anti-fibrotic strategies have shown promise in preclinical models yet failed to demonstrate clear clinical…
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 →2022ReviewNon-viral Gene Delivery
Le Tmd, Yoon A-R, Thambi T, Yun C-O
Cancer immunotherapy — especially immune checkpoint inhibitors (ICIs), CAR-T cells, and oncolytic viruses (OVs) — has shown major clinical success but still faces low response rates, severe immune-related side effects, complex tumour microenvironment barriers, instability/short half-life of therapeutics, and high…
Read the article →Stem Cell Research & Therapy2021ReviewNon-viral Gene Delivery
Farough Marofi, Roza Motavalli, Vladimir A. Safonov, Lakshmi Thangavelu, Alexei Valerievich Yumashev, Markov Alexander, Navid Shomali, Max Stanley Chartrand, Yashwant Pathak, Mostafa Jarahian, Sepideh Izadi, Ali Hassanzadeh, Naghmeh Shirafkan, Safa Tahmasebi, Farhad Motavalli Khiavi
CAR T cell therapy has transformed treatment of hematologic malignancies, but its efficacy in solid tumours remains unsupported. Solid tumours present distinct barriers—antigen heterogeneity, poor T cell trafficking/infiltration, and an immunosuppressive tumour microenvironment (TME)—that limit CAR T cell function…
Read the article →Blood Cancer Journal2021ReviewNon-viral Gene Delivery
Robert C. Sterner, Rosalie M. Sterner
CAR-T cell therapy has produced remarkable clinical responses in certain B cell leukemias and lymphomas, but major limitations remain—including life-threatening toxicities, limited efficacy in solid tumours, antigen escape, poor persistence/trafficking, and an immunosuppressive microenvironment. This review addresses…
Read the article →Advanced Functional Materials2021ReviewNon-viral Gene Delivery
Zhaoting Li, Yixin Wang, Yingyue Ding, Lauren Repp, Glen S. Kwon, Quanyin Hu
Immunotherapy has limited response rates and systemic side effects, and synthetic drug delivery systems can be immunogenic and toxic. Cell-based delivery systems—using endogenous cells as natural carriers—offer low immunogenicity, low toxicity, improved biocompatibility, active tissue targeting, and the ability to…
Read the article →EBioMedicine* (Elsevier)2021ReviewNon-viral Gene Delivery
Ella S. Atsavapranee, Margaret M. Billingsley, Michael J. Mitchell
Adoptive T cell therapy has been revolutionized by genetic engineering, but viral transduction—the standard delivery method—has limitations including small cargo capacity, high immunogenicity, high manufacturing cost, and risks of genotoxicity/insertional mutagenesis. There is a need for improved non-viral delivery…
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 →