Molecular cancer2026ResearchNon-viral Gene DeliveryDrug Delivery
Ni J, He G, Wang H, Qin Y, Guo J, Wang Y, Et Al.
Proficient mismatch repair/microsatellite-stable colorectal cancer (pMMR/MSS CRC), which represents the majority of clinical cases, exhibits low tumor mutational burden and minimal responsiveness to immune checkpoint blockade. Disrupting the MMR system has been shown to resensitize pMMR/MSS CRC to immune…
Read the article →Journal of drug targeting2026ReviewNon-viral Gene Delivery
Khan Ms, Abourehab Mas, Gupta G, Goh Kw, Sahebkar A, Kesharwani P
Breast cancer progression is driven by molecular heterogeneity, drug resistance (DR), and interactions within the tumour microenvironment (TME), creating an urgent need for therapies that can selectively suppress disease-associated genes. Small interfering RNA (siRNA) can silence targets involved in tumour growth…
Read the article →International journal of pharmaceutics: X2026ResearchNon-viral Gene DeliveryDrug Delivery
Kim Kh, Mainali A, Pih Sh, Jung Hs, Kim Hj, Kim Na, Et Al.
RNA-loaded lipid nanoparticles (LNPs) are highly sensitive to temperature fluctuations, which present significant challenges for storage and transportation. Lyophilization is a potential strategy to enhance storage stability; however, the freeze-drying process can subject nanoparticles to stresses that may alter…
Read the article →Molecular pharmaceutics2026ResearchNon-viral Gene DeliveryDrug Delivery
Gul S, Vergnaud J, Wang Q, Hery M, Dumont F, Tran P, Et Al.
Tumor-associated macrophages (TAMs) are central regulators of the tumor microenvironment (TME). Their polarization state can critically influence tumor development and treatment resistance. In the TME, the pro-tumor M2-like phenotype is the most prevalent among TAMs and contributes to tumor progression by promoting…
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 →International journal of nanomedicine2026ReviewNon-viral Gene DeliveryDrug Delivery
Thalij Km, You Hw, Habeeb M, Ratchagar Jv, Khot Vs, Gorde Pl
Hepatocellular carcinoma is the sixth most common cancer worldwide and a leading cause of cancer related mortality. Risk factors include chronic hepatitis B/C, obesity, alcohol abuse, diabetes and metabolic disorders. In advanced stages, normal treatments such as surgery, transplantation and chemotherapy are not as…
Read the article →BioDrugs2026ReviewNon-viral Gene DeliveryDrug Delivery
U Iqbal, Rw Hwang, Wj Costain
A review of blood–brain barrier transport mechanisms and emerging lipid nanoparticle strategies for carrying nucleic acid and other complex therapies into the central nervous system.
Read the article →Small2025ReviewNon-viral Gene DeliveryDrug Delivery
S Sarmah, S Baidya, M De
This review surveys lipid nanoparticle composition, ionisable lipid synthesis and strategies to target delivery of fragile RNA therapeutics while addressing tissue selectivity and immune activation.
Read the article →Molecular Therapy Methods & Clinical Development2025ReviewNon-viral Gene Delivery
Ca Brimacombe, Ja Kulkarni, Mhy Cheng, K An, D Witzigmann, Pr Cullis
A review of the physical principles and development history behind siRNA lipid nanoparticles for liver gene silencing and mRNA lipid nanoparticles for protein expression.
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 →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 →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
Maeki M, Uno S, Niwa A, Okada Y, Tokeshi M
RNA-loaded lipid nanoparticles (LNPs) are clinically validated for siRNA and mRNA delivery, but their therapeutic performance depends critically on reproducible control of size, size distribution, zeta potential, and RNA encapsulation efficiency. Microfluidic devices offer precise mixing, rapid ethanol dilution, high…
Read the article →Chemical Society Reviews* (as indicated by review format; exact volume/pages and DOI not included in the supplied file)2021ReviewNon-viral Gene Delivery
Yingshu Guo, Xiuping Cao, Xiaofei Zheng, Sk Jahir Abbas, Juan Li, Weihong Tan
Cancer treatment still relies heavily on chemotherapy, which causes severe damage to normal cells and systemic side effects. Safer, more selective drug delivery strategies are needed. Nanocarriers based on nucleic acids (NCNAs) are attractive because nucleic acids offer biocompatibility, low toxicity, programmable…
Read the article →Nature Reviews Drug Discovery2021ReviewDrug Delivery
Michael J. Mitchell, Margaret M. Billingsley, Rebecca M. Haley, Marissa E. Wechsler, Nicholas A. Peppas, Robert Langer
Nanoparticle (NP) research has generated promising preclinical results, but clinical translation remains limited. A major barrier is the mismatch between one-size-fits-all NP designs and the heterogeneous biological barriers across patients and diseases. Precision medicine offers patient stratification, but precision…
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 →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 →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 →Nano Letters2021ResearchNon-viral Gene Delivery
Sarah J. Shepherd, Claude C. Warzecha, Sagar Yadavali, Rakan El-Mayta, Mohamad-Gabriel Alameh, Lili Wang, Drew Weissman, James M. Wilson, David Issadore, Michael J. Mitchell
Microfluidic mixing can produce precise LNPs but is limited in throughput, while bulk mixing is scalable but yields larger, heterogeneous particles with variable potency. A scalable microfluidic device is needed to produce potent RNA-LNPs across discovery and clinical scales. PMD achieved 18.4 L/h production…
Read the article →Advanced Science (Weinh.)2021ResearchNon-viral Gene Delivery
Johan Karlsson, Stephanie Y. Tzeng, Shayan Hemmati, Kathryn M. Luly, Olivia Choi, Yuan Rui, David R. Wilson, Kristen L. Kozielski, Alfredo Quiñones-Hinojosa, Jordan J. Green
Systemic delivery of RNA therapeutics with polymer-based nanocarriers is limited by poor colloidal stability in blood and inefficient intracellular delivery of siRNA to the cytosol. There is a need for nanoparticles that remain stable extracellularly but rapidly release RNA intracellularly. Crosslinking: Molecular…
Read the article →International Journal of Polymeric Materials and Polymeric Biomaterials2021ResearchNon-viral Gene Delivery
Liu T, Lin M, Wu F, Lin A, Luo D, Zhang Z
siRNA therapeutics are limited by poor cellular uptake, serum nuclease degradation, and inefficient endosomal/lysosomal escape. Chitosan is biocompatible and biodegradable but has low transfection efficiency, largely due to poor buffering capacity and weak endosomal escape. Histidine grafting was explored to add…
Read the article →Signal Transduction and Targeted Therapy2021ReviewNon-viral Gene Delivery
Chen L, Hong W, Ren W, Xu T, Qian Z, He Z.
Synthetic nanoparticles face physiological barriers, RES clearance, and unintended biological interactions despite PEGylation and ligand grafting. Biological vectors—cell membranes, extracellular vesicles (EVs), and viruses—offer biocompatibility, biodegradability, immune evasion, and natural targeting. This review…
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