Journal of Materials Chemistry B2020ResearchNon-viral Gene Delivery
Yana Tarakanchikova, Albert Muslimov, Igor Sergeev, Kirill Lepik, Nikita Yolshin, Alexander Goncharenko, Kirill Vasilyev, Igor Eliseev, Anton Bukatin, Vladislav Sergeev, Sergey Pavlov, Alexey Popov, Igor Meglinski, Boris Afanasyev, Bogdan Parakhonskiy, Gleb Sukhorukov, Dmitry Gorin
DNA- and mRNA-based therapies are transforming biomedicine, but intracellular delivery—especially to hard-to-transfect, clinically relevant cells such as primary human T lymphocytes—remains a major barrier. Existing non-viral methods often suffer from low transfection efficiency, high toxicity, or complex…
Read the article →Nature Communications2020ResearchNon-viral Gene Delivery
Siddharth Patel, N. Ashwanikumar, Ema Robinson, Yan Xia, Cosmin Mihai, Joseph P. Griffith Iii, Shangguo Hou, Adam A. Esposito, Tatiana Ketova, Kevin Welsher, John L. Joyal, Örn Almarsson, Gaurav Sahay
Endosomal sequestration of lipid-based nanoparticles (LNPs) remains a formidable barrier to delivery, with only <2% of LNPs reaching the cytosol. The role of cholesterol structure in LNP-mediated mRNA delivery and endosomal escape was poorly understood. There is a need to decode the structural characteristics of…
Read the article →Nanomedicine2020ResearchNon-viral Gene Delivery
John Choi, Yuan Rui, Jayoung Kim, Noah Gorelick, David R. Wilson, Kristen Kozielski, Antonella Mangraviti, Eric Sankey, Henry Brem, Betty Tyler, Jordan J. Green, Eric M. Jackson
Medulloblastoma (MB) and atypical teratoid/rhabdoid tumour (AT/RT) are common paediatric brain malignancies. Radiation carries high risks of developmental sequelae in young children, and current treatments remain inadequate. Viral gene therapy has safety concerns in paediatric patients, so a safe, effective nonviral…
Read the article →Nature Biotechnology2020ResearchNon-viral Gene Delivery
David N. Nguyen, Theodore L. Roth, P. Jonathan Li, Peixin Amy Chen, Ryan Apathy, Murad R. Mamedov, Linda T. Vo, Victoria R. Tobin, Daniel Goodman, Eric Shifrut, Jeffrey A. Bluestone, Jennifer M. Puck, Francis C. Szoka, Alexander Marson
CRISPR-Cas9 genome editing in clinically relevant primary cells is limited by inefficient homology-directed repair (HDR) and cytotoxicity of exogenous DNA. Improvements are needed to increase editing efficiency, cell viability, and generalizability across cell types for adoptive cell therapies and research. tCTS…
Read the article →International Journal of Nanomedicine2020ResearchNon-viral Gene Delivery
CAR-T cell therapy is limited by complex manufacturing, viral vector use, high cost, and severe toxicities. A nonviral, transient CAR modification approach using self-assembled nanoparticles could provide a simpler, safer, and potentially broadly applicable alternative for T-cell engineering. Formulation screening…
Read the article →Frontiers in Bioengineering and Biotechnology2020ResearchDrug Delivery
Serkan Yaman, Harish Ramachandramoorthy, Gizem Oter, Daria Zhukova, Tam Nguyen, Manoj K. Sabnani, Jon A. Weidanz, Kytai T. Nguyen
Melanoma is an aggressive skin cancer with limited treatment efficacy due to non-specific drug targeting, severe side effects, and multidrug resistance. Current cell-based immunotherapies are costly, complex, and carry long-term autoimmune risks. There is a need for a targeted, biocompatible drug delivery system that…
Read the article →ACS Biomaterials Science & Engineering (as indicated in the supplied file header; exact volume/pages and DOI were not in2020ResearchNon-viral Gene Delivery
Denis Routkevitch, Deepti Sudhakar, Marranne Conge, Mahita Varanasi, Stephany Y. Tzeng, David R. Wilson, Jordan J. Green
The mechanism by which cationic polymers with titratable amines mediate endosomal escape and cytosolic delivery of nucleic acids remains poorly understood. Buffering capacity alone has often failed to predict transfection efficacy, so the study examines whether the effective pKa of poly(beta-amino ester)s (PBAEs)…
Read the article →Molecular Therapy: Nucleic Acids2020ResearchNon-viral Gene Delivery
Rui Yan Yuan, Mahita Varanasi, Shanelle Mendes, Hannah M. Yamagata, David R. Wilson, Jordan J. Green
CRISPR-Cas9 gene editing requires efficient intracellular delivery of large cargo. Viral vectors have packaging and production limitations, and nonviral CRISPR plasmid delivery had mainly been studied for single-site knockout, not for gene deletion requiring two cleavage events. The transfection requirements for…
Read the article →Frontiers in Molecular Biosciences2020ReviewDrug Delivery
Yao Y, Zhou Y, Liu L, Xu Y, Chen Q, Wang Y, Wu S, Deng Y, Zhang J, Shao A.
Conventional chemotherapy and targeted therapy are limited by systemic toxicity, poor tumour targeting, and multidrug resistance (MDR). Nanoparticle-based drug delivery offers improved pharmacokinetics, biocompatibility, enhanced permeability and retention (EPR), precise targeting, and potential to overcome…
Read the article →Journal of Oncology2020ReviewDrug Delivery
Zein R, Sharrouf W, Selting K.
Drug penetration into tumours is limited by abnormal vasculature and high interstitial pressure, and chemotherapy causes undesirable adverse effects including bone marrow and gastrointestinal toxicity. Nanotechnology-based drug delivery systems aim to reduce these adverse effects by enhancing penetration and…
Read the article →2020ReviewNon-viral Gene Delivery
Zeb A, Rana I, Choi H-I, Et Al.
Biopharmaceuticals have become clinically and commercially important due to their specificity, potency, targeting ability, and reduced side effects, but their macromolecular structure and intrinsic instability make formulation and administration challenging; parenteral delivery remains the only viable option in most…
Read the article →Nanomaterials2020ReviewDrug Delivery
Fam Sy, Chee Cf, Yong Cy, Ho Kl, Mariatulqabtiah Ar, Tan Ws.
Nanoparticles (NPs) interact extensively with plasma proteins after intravenous administration and are rapidly cleared by the mononuclear phagocyte system (MPS) or complement system, causing premature drug release at off-target sites. A stealth coating layer can improve blood circulation half-life by escaping immune…
Read the article →Nature Communications2020ReviewNon-viral Gene Delivery
Karen Bulaklak And Charles A. Gersbach
Gene therapy is at an inflection point: recent approvals and clinical successes have validated the field, but broader application is still limited by immune responses to vectors, inefficient delivery outside the retina and liver, and regulatory frameworks that are poorly suited to personalised, potentially curative…
Read the article →Frontiers in Chemistry2020ReviewNon-viral Gene Delivery
Guevara Ml, Persano F, Persano S
mRNA is a flexible and potentially safer cancer immunotherapy platform, but its clinical use has been limited by extracellular instability, poor cellular uptake, and inefficient endosomal escape. Lipid nanoparticles have become the most advanced non-viral delivery system for mRNA, enabling therapeutic vaccines…
Read the article →Bioconjugate Chemistry2020ReviewNon-viral Gene Delivery
Francia V, Schiffelers Rm, Cullis Pr, Witzigmann D
LNPs are clinically advanced vectors for siRNA, mRNA, and DNA delivery, but their in vivo behaviour is strongly influenced by the biological environment. Upon administration, biomolecules adsorb to the LNP surface and form a “biomolecular corona,” which defines the particle’s biological identity, affects stability…
Read the article →Expert Opinion on Drug Delivery2020ReviewNon-viral Gene Delivery
Karlsson, J.; Rhodes, K. R.; Green, J. J.; Tzeng, S. Y
Non-viral gene delivery needs safe and efficient carriers. PBAEs are biodegradable cationic polymers with promising transfection activity, but they face challenges such as instability in physiological fluids, positive-charge toxicity, and limited systemic delivery. This review summarises PBAE properties, advantages…
Read the article →Oncology Reports2019ReviewNon-viral Gene Delivery
Rimjhim Mohanty, Chitran Roy Chowdhury, Solomon Arega, Prakriti Sen, Pooja Ganguly, Niladri Ganguly
Cancer is a leading cause of mortality worldwide, and conventional treatments and cytotoxic immunotherapies have limitations. Because tumours are complex and involve multiple genetic and cellular factors in tumorigenesis and metastasis, there is a need for an immunotherapy that targets tumours at both cellular and…
Read the article →Molecular Therapy2019ReviewNon-viral Gene Delivery
Piotr S. Kowalski, Arnab Rudra, Lei Miao, Daniel G. Anderson
mRNA has broad therapeutic potential for vaccination, protein replacement, and gene editing, but its clinical translation is limited by the need for improved intracellular delivery systems. mRNA is much larger than siRNA or ASOs (~300–5,000 kDa, ~1–15 kb vs ~14 kDa and 4–10 kDa, respectively), making delivery more…
Read the article →Nature Reviews Drug Discovery.2019ReviewNon-viral Gene Delivery
Rachel S. Riley, Carl H. June, Robert Langer, Michael J. Mitchell.
Immunotherapy has become powerful but broad implementation limited by inability to control immune modulation; serious adverse effects including autoimmunity, nonspecific inflammation. Need delivery technologies to improve efficacy and safety. Numbers.
Read the article →Nature Reviews Immunology2019ReviewNon-viral Gene Delivery
Søren R. Paludan, Line S. Reinert, Veit Hornung
DNA in abnormal cellular compartments (cytosol, endosomes, micronuclei) is a potent danger signal for the innate immune system, primarily known for inducing type I interferons and IL-1β. More recently, it has become clear that cytosolic DNA also triggers various forms of programmed cell death (PCD), but the pathways…
Read the article →Biophysical Journal2019ResearchNon-viral Gene Delivery
Janusz Khetan, Madhan Srikar, Daniel B. Forger, Sutapa Barua
The general perception is that cellular uptake of materials is proportional to cell volume (mass) or surface area, following cubic or square relationships with cell radius. However, experimental data on nanoparticle uptake in MDA-MB 231 breast cancer cells show a linear relationship with cell radius—a result that is…
Read the article →Nature2019ResearchNon-viral Gene Delivery
Haig Aghajanian, Toru Kimura, Joel G. Rurik, Aidan S. Hancock, Michael S. Leibowitz, Li Li, John Scholler, James Monslow, Albert Lo, Wei Han, Tao Wang, Kenneth Bedi, Michael P. Morley, Ricardo A. Linares Saldana, Nikhita A. Bolar, Kendra Mcdaid, Charles-Antoine Assenmacher, Cheryl L. Smith, Dagmar W
Fibrosis is observed in nearly every form of myocardial disease and contributes to heart failure, yet clinical interventions targeting fibrosis remain limited. No therapies directly target excessive cardiac fibrosis, and very few interventions improve cardiac function in patients with impaired compliance. Genetic…
Read the article →Nanoscale2019ResearchNon-viral Gene Delivery
Dongyu Chen, Neha Parayath, Shanthi Ganesh, Weimin Wang, Mansoor Amiji
The protein corona that forms on lipid nanoparticles (LNPs) after systemic administration can alter their biological identity, but its impact on tumour delivery is not well understood. This study aimed to determine whether LNP formulation composition and surface charge can manipulate the protein corona and thereby…
Read the article →Nanoscale2019ResearchNon-viral Gene Delivery
Dongyu Chen, Shanthi Ganesh, Weimin Wang, Mansoor Amiji
Protein corona formation in biological fluids can alter nanoparticle cellular uptake, transfection, and gene silencing, but the relationship between LNP surface chemistry and corona-mediated delivery is incompletely understood. This study examined how PEG lipid chain length and PEG molar ratio affect protein corona…
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