Exploration of Medicine2021ReviewNon-viral Gene Delivery
Sureshbabu Ram Kumar Pandian, Clayton Fernando Rencllin, Krishnan Sundar
Conventional cancer immunotherapies (checkpoint inhibitors, CAR T cells) are effective but expensive, cause adverse side effects, and face challenges in solid tumours. Nanomaterials offer advantages in delivery, diagnostics, and immune modulation, but a comprehensive understanding of how different nanomaterial types…
Read the article →ACS Nano2021ReviewDrug Delivery
Paula M. Cevaal, Abdalla Ali, Ewa Czuba-Wojnilowicz, Jori Symons, Sharon R. Lewin, Christina Cortez-Jugo, Frank Caruso
T cells are attractive targets for immunotherapy, cancer, HIV, autoimmunity, and inflammation, but nanoparticle delivery to T cells remains a major technological challenge due to their nonphagocytic nature and multiple physiological barriers. There is a need for rational design principles for in vivo T cell-targeting…
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 →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 →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 →Nature Communications2021ResearchNon-viral Gene Delivery
Julia Koerner, Dennis Horvath, Valerie L. Herrmann, Anna Mackeracher, Bruno Gander, Hideo Yagita, Jacques Rohayem, Marcus Groettrup
Cancer immunotherapy needs potent, pharmaceutically defined, GMP-compatible adjuvants for clinical translation. Poly(I:C) is a widely used TLR3 agonist but has ill-defined structure, heterogeneity, pyrogen contamination, and toxicity concerns. Riboxxim is a well-defined 100-bp double-stranded RNA with a…
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 →Advanced Healthcare Materials2021ReviewNon-viral Gene Delivery
Raza F, Zafar H, Zhang S, Kamal Z, Su J, Yuan W-E, Qiu M.
Cancer immunotherapy is limited by the immunosuppressive tumour microenvironment, patient heterogeneity, poor delivery of immunotherapeutics, and systemic immunotoxicity. Cell membrane-derived biomimetic nanoparticles may improve delivery and biodistribution, enhance targeting and immune stimulation, and overcome…
Read the article →Advanced Drug Delivery Reviews2021ReviewNon-viral Gene Delivery
Kim J, Eygeris Y, Gupta M, Sahay G.
mRNA vaccines are promising but naked mRNA is fragile, susceptible to enzymatic degradation, poorly taken up by cells due to electrostatic repulsion, and can trigger innate immune responses. Self-assembly offers a versatile approach to prepare delivery vehicles with customisable properties. The review discusses…
Read the article →Bioactive Materials2021ReviewNon-viral Gene Delivery
Muyue Yang, Jipeng Li, Ping Gu, Xianqun Fan
Tumour microenvironment (TME) modulation is a promising strategy in cancer immunotherapy, but conventional immunotherapeutic agents suffer from limited drug retention in the TME, severe adverse events, and low response rates. Nanoparticles can prolong retention, enable targeted delivery to TME components, and convert…
Read the article →Molecules2021ReviewNon-viral Gene Delivery
Wan, Z.; Zheng, R.; Moharil, P.; Liu, Y.; Chen, J.; Sun, R.; Song, X.; Ao, Q
Cancer immunotherapy can produce durable clinical responses, but systemic delivery of immunostimulatory agents is limited by short half-lives, off-target toxicities (e.g., cytokine release syndrome), low response rates (10–30%), and poor efficacy in solid tumours. Polymeric micelles offer a biocompatible, modifiable…
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 →Angewandte Chemie International Edition2020ReviewNon-viral Gene Delivery
Shuangqian Yan, Zichao Luo, Zhenglin Li, Yu Wang, Jun Tao, Changyang Gong, Xiaogang Liu
Cancer immunotherapy has improved clinical outcomes, but few patients show adequate response rates and long-term responses, and systemic side effects remain common due to the dynamic nature of the immune system. Biomaterial-assisted immunotherapy is a promising approach to improve therapeutic efficacy and reduce side…
Read the article →PNAS* (*Proceedings of the National Academy of Sciences*)2020ReviewNon-viral Gene Delivery
Stephany Y. Tzeng, Kisha K. Patel, David R. Wilson, Randall A. Meyer, Kelly R. Rhodes, Jordan J. Green
Cancer immunotherapy has shown clinical success but remains limited by low response rates, high cost, and the need for ex vivo cell manipulation or prior knowledge of patient-specific tumour antigens. A broadly applicable, antigen-agnostic strategy that genetically reprograms tumour cells in situ—without ex vivo…
Read the article →Acta Biomaterialia (Published by Elsevier Ltd on behalf of Acta Materialia Inc.)2020ResearchNon-viral Gene Delivery
Kelly R. Rhodes, Randall A. Meyer, Justin Wang, Stephany Y. Tzeng, Jordan J. Green
Regulatory T cell (Treg)-based therapeutics show promise for treating autoimmune diseases and preventing transplant rejection, but adoptive Treg transfer is expensive, complex, and difficult to implement. "Off-the-shelf" non-cellular alternatives that can induce endogenous Tregs in vivo are needed. Existing…
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…
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