Pathology, research and practice2026ResearchNon-viral Gene DeliveryDrug Delivery
Dong Y, Li Q, Ou Y, Li M, Liu N, Wang X, Et Al.
Neutralizing antibodies act rapidly against SARS-CoV-2, but monoclonal antibodies are costly to manufacture and single-domain antibodies are cleared rapidly. Here we evaluated an mRNA-lipid nanoparticle (LNP) platform encoding the neutralizing nanobody VHH 72 and optimized the carrier by raising DSPC from 10 to 40…
Read the article →International journal of pharmaceutics2026ResearchNon-viral Gene DeliveryDrug Delivery
Miyazaki T, Kubara K, Kondo K, Kamiyama H, Hara S, Moriya J, Et Al.
mRNA-lipid nanoparticles (LNP) have emerged as a versatile modality, enabling diverse applications by changing encoded mRNA sequences. However, the conventional mRNA-LNP preparation process poses significant barriers to non-specialists because it requires specialized equipment and technical expertise. In this study…
Read the article →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 →Journal of controlled release : official journal of the Controlled Release Society2026ResearchNon-viral Gene DeliveryDrug Delivery
Li P, Abdallah M, Yao Y, Mugan Rs, Payne Tj, Fabb Sa, Et Al.
Lipid nanoparticle (LNP) formulations have enabled the in vivo delivery of messenger ribonucleic acid (mRNA) vaccines and therapeutics yet the delivery of RNA remains relatively inefficient. In order to improve LNP design there is a need to better understand how current mRNA-LNP formulations are trafficked and…
Read the article →Theranostics2026ResearchNon-viral Gene DeliveryDrug Delivery
Lu Y, Cai X, Li Y, Lv Y, Tang Y, Li Y, Et Al.
Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising strategy for management of relapsed/refractory acute myeloid leukemia (R/R AML). Safety and preliminary activity of CD38-targeted CAR-T cells in R/R AML were demonstrated in our prior study; however, relapse with CD38-positive blasts persisted…
Read the article →Nano letters2026ResearchNon-viral Gene DeliveryDrug Delivery
Liu H, Yang B, Chen S, Li Y, Zhang Y, Huang Y, Et Al.
Highly efficient lung-selective mRNA delivery is pivotal for advancing mRNA-based targeted therapy. Here, we report bis(phosphoramidate diester)-based ionizable cationic lipids (bpLs) for lung-specific mRNA delivery via a distinct intercellular transport mechanism. A bpL library is synthesized by modular headgroups…
Read the article →ACS nano2026ResearchNon-viral Gene DeliveryDrug Delivery
Abbasi S, Bockley Km, Dohr J, Chen E, Carter Dm, Berlinicke Ca, Et Al.
Active targeting can improve the efficacy of mRNA therapeutics, but ligand-mediated targeting with lipid nanoparticles (LNPs) remains challenging. Here, we studied the impact of polyethylene glycol (PEG)-lipid composition and triantennary N-acetylgalactosamine (TriGalNAc)-modification on the hepatic delivery…
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 →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 →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 →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 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 →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 →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…
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