Molecular therapy. Oncology2026ReviewNon-viral Gene DeliveryDrug Delivery
Bedada At, Genet S
Cancer remains a formidable global health challenge, representing the second leading cause of mortality worldwide. In 2023, there were approximately 18.5 million new cancer cases and over 10 million deaths globally, with projections estimating 30.5 million new cases and 18.6 million deaths annually by 2050. In the…
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 →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 →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 →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 →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 →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 →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 →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 →Leukemia2021ResearchDrug Delivery
Kinan Alhallak, Jennifer Sun, Katherine Wasden, Nicole Guenthner, Julie O'neal, Barbara Muz, Justin King, Daniel Kohnen, Ravi Vij, Samuel Achilefu, John F. Dipersio, Abdel Kareem Azab
T-cell-based immunotherapies such as CAR-T cells and bispecific T-cell engagers (BiTEs) have shown promise but have significant limitations: (1) poor pharmacokinetics requiring continuous infusion (BiTE half-life ~2 h), and (2) single-antigen targeting leading to antigen-loss tumour escape and relapse. A modular…
Read the article →Drug Delivery and Translational Research2021ResearchDrug Delivery
Yuan Rui, Jordan J. Green
Glioblastoma (GBM) is one of the deadliest primary adult tumours with a median survival of only 14.6 months post-diagnosis, a statistic that has changed little in two decades. While cancer immunotherapy has shown remarkable progress in other solid tumours, the blood-brain barrier (BBB) and the immune-privileged…
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 →Nature Reviews Drug Discovery2021ReviewNon-viral Gene Delivery
Chaudhary N, Weissman D, Whitehead Ka.
mRNA vaccines have progressed from a scepticism-inducing idea to clinical reality, with COVID-19 catalysing the fastest vaccine development in history. Remaining needs include optimising mRNA design, intracellular delivery, and applications beyond SARS-CoV-2 prophylaxis. This review describes mRNA vaccine…
Read the article →Nature Nanotechnology2021ReviewNon-viral Gene Delivery
Gong N, Sheppard Nc, Billingsley Mm, June Ch, Mitchell Mj.
T-cell-based immunotherapies have shown clinical success in B-cell malignancies, but broad implementation is limited by insufficient T-cell expansion, poor trafficking into solid tumours, T-cell exhaustion in hostile tumour microenvironments, and loss of target antigen expression. Nanomaterials may uniquely overcome…
Read the article →2021ReviewDrug Delivery
Cancer immunotherapy has shown efficacy but is limited by serious adverse effects, nonspecific inflammation, and challenges in spatiotemporal control of immune responses. Nanomedicine and functionalised nanosystems offer programmable pharmacokinetics, co-delivery of immunomodulators, and targeted delivery…
Read the article →2021ReviewDrug Delivery
Venkatas J, Singh M.
Cervical cancer is immunologically relevant because retained high-risk HPV antigens can be recognised as foreign, making immunotherapy attractive. However, conventional immunotherapy is limited by variable efficacy, immune evasion, cytokine toxicity, and poor targeting. Nanomedicine may improve delivery, targeting…
Read the article →Frontiers in Immunology2021ReviewNon-viral Gene Delivery
Balakrishnan Pb, Sweeney Ee.
Adoptive T cell therapy has revolutionized treatment of some hematologic malignancies but remains limited in solid tumours—especially central nervous system (CNS) tumours—by poor intratumoral delivery across anatomical barriers, suboptimal T cell specificity or activation, and intratumoral T cell dysfunction caused…
Read the article →Seminars in Immunology2021ReviewNon-viral Gene Delivery
Est-Witte Se, Livingston Nk, Omotoso Mo, Green Jj, Schneck Jp.
T cell therapies (TIL, TCR, CAR T) show clinical efficacy but are limited by high cost, lengthy ex vivo manufacturing, patient variability, and poor persistence. Nanoparticles offer a modular, universal platform to improve T cell therapy at every stage—from antigen presentation and T cell activation to T cell…
Read the article →Blood Advances2020ReviewNon-viral Gene Delivery
Annika M. Frank, Angela H. Braun, Lea Scheib, Shivani Agarwal, Irene C. Schneider, Floriane Fusil, Severine Perian, Ugur Sahin, Frederic B. Thalheimer, Els Verhoeyen, Christian J. Buchholz
Conventional lentiviral vectors (LVs) are not selective for T cells and cannot efficiently transduce resting or minimally stimulated T lymphocytes, which limits their use for direct in vivo T-cell gene delivery. There is a need for vectors that can both target T cells specifically and activate them sufficiently to…
Read the article →