Nature Communications2020ResearchNon-viral Gene Delivery
John C. Charpentier, Di Chen, Philip E. Lapinski, Jackson Turner, Irina Grigorova, Joel A. Swanson, Philip D. King
Macropinocytosis has been shown to regulate the growth of Ras-transformed tumour cells under amino acid (AA)-limiting conditions by providing extracellular proteins that are degraded into AA to fuel cell growth and activate mTORC1. However, whether macropinocytosis regulates the growth of non-transformed mammalian…
Read the article →Cancers (MDPI)2020ResearchNon-viral Gene Delivery
Julie J.-J. Tang, Alina P. Sung, Mariel J. Guglielmo, Laura N.-G., Doug Redelman, James Smith-Gagen, Diane Hudig
Monoclonal antibody anti-tumour therapies rely on NK cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC), but patient responses vary widely. While tumour antigen escape is one cause of treatment failure, the role of inter-individual variation in NK cell serial killing capacity—the ability of a single…
Read the article →Cancer Immunology Research (AACR)2020ResearchNon-viral Gene Delivery
Dylan J. Drakes, Sarwish Rafiq, Terence J. Purdon, Andrea V. Lopez, Smita S. Chandran, Christopher A. Klebanoff, Renier J. Brentjens
T-cell receptor (TCR)-modified T-cell gene therapy can target a variety of extracellular and intracellular tumour-associated antigens, yet has had little clinical success. A potential explanation for limited antitumor efficacy is a lack of T-cell activation in vivo, particularly when tumour cells downregulate…
Read the article →Journal of Controlled Release2020ResearchNon-viral Gene Delivery
Pedro P. Guimaraes, Rui Zhang, Roman Spektor, Mingchee Tan, Amanda Chung, Margaret M. Billingsley, Rakan El-Mayta, Rachel S. Riley, Lili Wang, James M. Wilson, Michael J. Mitchell
LNP libraries are usually screened in vitro, which poorly predicts in vivo mRNA delivery. A high-throughput in vivo platform was needed to screen many LNP formulations simultaneously and identify lead carriers for functional mRNA delivery. b-mRNA could be detected in liver at doses as low as 17 ng; b-mRNA delivery…
Read the article →Science Advances2020ResearchNon-viral Gene Delivery
Elana Ben-Akiva, Randall A. Meyer, Hongzhe Yu, Jonathan T. Smith, Drew M. Pardoll, Jordan J. Green
Previous red blood cell (RBC) membrane-coated nanoparticles have all been spherical, missing the physical shape component of biomimicry. Particle shape is a critical design parameter affecting biodistribution, macrophage evasion, and targeted interactions. A platform combining physical biomimicry (anisotropic shape)…
Read the article →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 →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 →International Journal of Nanomedicine2020ReviewNon-viral Gene Delivery
Chen, C.-K.; Huang, P.-K.; Law, W.-C.; Chu, C.-H.; Chen, N.-T.; Lo, L.-W
Gene therapy is limited by the fragile nature of therapeutic DNA/RNA and by safety concerns with viral vectors. Non-viral polymeric vectors are attractive, but conventional cationic polymers such as PEI, PDMAEMA, and PLL are often non-degradable, causing accumulation, cytotoxicity, and poor gene unpacking. This…
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 →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 →Journal of Controlled Release2019ResearchNon-viral Gene Delivery
Yusuke Sato, Kazuki Hashiba, Kosuke Sasaki, Masatoshi Maeki, Manabu Tokeshi, Hideyoshi Harashima
Endosomal escape remains a major rate-limiting step for siRNA delivery. The structure–activity relationships (SAR) of pH-sensitive cationic lipids were incompletely understood, limiting rational design of lipid nanoparticles (LNPs) for efficient in vivo siRNA delivery to hepatocytes. Hydrophilic head group structure…
Read the article →Nature Communications2019ResearchNon-viral Gene Delivery
Francesca Giulimondi, Luca Digiacomo, Daniela Pozzi, Sara Palchetti, Elisabetta Vulpis, Anna Laura Capriotti, Riccardo Zenezini Chiozzi, Aldo Laganà, Heinz Amenitsch, Laura Masuelli, Giovanna Peruzzi, Morteza Mahmoudi, Isabella Screpanti, Alessandra Zingoni
Liposome clinical translation is limited by opsonisation and rapid clearance by immune cells. Although the protein corona is recognised as the liposome’s “biological identity,” it was unclear whether pre-adsorbed corona proteins could help liposomes avoid capture by circulating leukocytes in whole blood and thereby…
Read the article →Biomaterials Science2019ResearchNon-viral Gene Delivery
Brynn R. Olden, Emmeline Cheng, Yilong Cheng, Suzie H. Pun
T cells are an important target for ex vivo gene delivery and editing, but most commercial reagents cannot transfect them and cationic polymers show only moderate success. The specific intracellular barriers limiting non-viral gene delivery to human T cells are poorly understood, hindering rational polymer design…
Read the article →Acta Biomaterialia2019ResearchNon-viral Gene Delivery
Zuoying Yuan, Pengfei Wei, Yiqian Huang, Wenxin Zhang, Fuyu Chen, Xu Zhang, Jianping Mao, Dafu Chen, Qing Cai, Xiaoping Yang
Magnesium ions (Mg²⁺) promote bone regeneration, but their effects are strongly concentration-dependent: too little has minimal effect, while excess Mg²⁺ can impair osteoblast activity and bone metabolism. There is no well-established bone tissue engineering scaffold that precisely controls local Mg²⁺ release…
Read the article →Molecular Pharmaceutics2019ResearchNon-viral Gene Delivery
Wilson, D. R., Rui, Y., Siddiq, K., Routkevitch, D., & Green, J. J. (2019).
Nonviral gene delivery remains limited by low transfection efficacy, especially under physiological serum conditions and at low nanoparticle doses. Although linear poly(β-amino ester)s (PBAEs) are effective, branching structure had not been systematically evaluated in well-defined PBAE-like poly(ester amine) systems…
Read the article →Journal of Pharmaceutical Investigation2019ReviewDrug Delivery
PLA and PLGA are FDA-approved, biodegradable polymers widely used for micro- and nanoparticle drug delivery, but their clinical performance depends on biocompatibility, degradation behaviour, and drug-release control. This review addresses the need to understand PLA/PLGA tissue responses, degradation pathways…
Read the article →Molecules2019ReviewNon-viral Gene Delivery
Thomas, T. J.; Tajmir-Riahi, H.-A.; Pillai, C. K. S
Gene therapy requires efficient delivery of genetic material, but viral vectors carry risks of immunogenicity, toxicity, and cancer formation. Cationic polymers such as polyethyleneimine (PEI) can condense DNA and facilitate delivery, but their lack of biodegradation causes significant toxicity due to polymer…
Read the article →Journal of King Saud University – Science2019ReviewDrug Delivery
Venditti, I
Polymeric nanocarriers such as dendrimers, micelles, nanoparticles, nanogels, nanocapsules, and vesicles are widely investigated for drug delivery, but their morphology, surface chemistry, and functionalisation strongly influence drug loading, controlled release, and targeting. This review addresses the need for a…
Read the article →Journal of Controlled Release2019ReviewNon-viral Gene Delivery
Cordeiro, R. A.; Serra, A.; Coelho, J. F. J.; Faneca, H
Gene therapy requires safe and effective delivery vectors. PBAEs are biodegradable cationic polymers with excellent gene delivery properties, but a comprehensive and critical overview of their use as gene carriers is lacking. This review provides the first comprehensive and critical overview of PBAE-based gene…
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