Nature Communications2018ResearchNon-viral Gene Delivery
Ewoud B. Compeer, Felix Kraus, Manuela Ecker, Gregory Redpath, Mayan Amiezer, Nils Rother, Philip R. Nicovich, Natasha Kapoor-Kaushik, Qiji Deng, Guerric P.B. Samson, Zhengmin Yang, Jieqiong Lou, Michael Carnell, Haig Vartoukan, Katharina Gaus, Jérémie Rossy
Polarized endocytic recycling of the T cell receptor (TCR) to the immunological synapse is essential for T cell activation, yet the cellular mechanisms that coordinate internalisation of surface receptors with sustained delivery back to the plasma membrane remain incompletely understood. The role of flotillins in…
Read the article →Drug Delivery2018ResearchDrug Delivery
Juan Chen, Xiaobing Yang, Liuqing Huang, Huixian Lai, Chuanhai Gan, Xuetao Luo
Lung cancer has the highest mortality among cancers, and single-agent chemotherapy is often unsuccessful due to drug resistance, insufficient intracellular uptake, nonspecific targeting, and severe systemic toxicity. Combination chemotherapy can suppress drug resistance and achieve synergistic anticancer efficacy…
Read the article →Proceedings of the National Academy of Sciences (PNAS)2018ResearchNon-viral Gene Delivery
Ole A. W. Haabeth, Timothy R. Blake, Colin J. Mckinlay, Robert M. Waymouth, Paul A. Wender, Ronald Levy
mRNA-based cancer vaccination is a promising approach for personalised immunotherapy, but safe and effective mRNA delivery remains a major challenge due to mRNA's instability and poor cell membrane permeability. While lipid nanoparticles (LNPs) are the primary delivery strategy, they have limitations with respect to…
Read the article →International Journal of Molecular Sciences2018ResearchNon-viral Gene Delivery
Simon A. B. Riedl, Alexander Raup, Patrick Kaiser, Christopher V. Synatschke, Valerie Jérôme, Ruth Freitag
Genetic modification of human T lymphocytes is critical for both basic research and emerging therapies (e.g., CAR-T cells), but established non-viral methods are highly inefficient. Linear polyethylenimine (l-PEI), the "gold standard" for non-viral transfection of mammalian cells, achieves only single-digit…
Read the article →Molecular Therapy2018ResearchNon-viral Gene Delivery
Daniel L. Jasinski, Hui Li, Peixuan Guo
Drugs with ideal pharmacokinetic profiles require long half-lives but little organ accumulation. Generally, these factors are contradictory: smaller particles lead to faster excretion and shorter half-lives, while larger particles lead to longer circulation but stronger organ accumulation and potential toxicity. The…
Read the article →Toxicology Research (RSC)2018ResearchNon-viral Gene Delivery
Shaohui Cui, Yueying Wang, Yan Gong, Xiao Lin, Yinan Zhao, Defu Zhi, Quan Zhou, Shubiao Zhang
Cationic lipids are widely used non-viral gene delivery vectors, but their toxicity remains a major bottleneck for clinical translation. Cytotoxicity is strongly associated with the cationic headgroup structure, yet the relationship between headgroup chemistry and toxic mechanisms has been rarely studied. IC50…
Read the article →PNAS2018ResearchNon-viral Gene Delivery
Colin J. Mckinlay, Nancy L. Benner, Ole A. Haabeth, Robert M. Waymouth, Paul A. Wender
Efficient mRNA delivery to lymphocytes remains a major unmet need for immunotherapy and vaccinology. Current methods rely largely on physical transfection such as electroporation, which is ex vivo, costly, and inefficient; chemical vectors generally achieve low lymphocyte mRNA transfection, especially in vivo. Lead…
Read the article →Pharmaceutical Research2018ResearchNon-viral Gene Delivery
Francesca Sacchetti, Gaetano Marverti, Domenico D’arca, Leda Severi, Eleonora Maretti, Valentina Iannuccelli, Salvatore Pacifico, Glauco Ponterini, Maria Paola Costi, Eliana Leo
PEGylated pH-sensitive liposomes may improve delivery of anti-cancer peptides, but PEGylation can reduce cellular uptake and endosomal escape (“PEG dilemma”), and it was unknown whether PEGylated liposome components interfere with the intracellular mechanism of action of the delivered drug. Physicochemical…
Read the article →Molecular Pharmaceutics (Just Accepted Manuscript)2018ResearchNon-viral Gene Delivery
David P. Walsh, Robert D. Murphy, Angela Panarella, Rosanne M. Raftery, Brenton Cavanagh, Jeremy C. Simpson, Fergal J. O’brien, Andreas Heise, Sally-Ann Cryan
Tissue engineering needs efficient, biocompatible non-viral gene delivery to mesenchymal stem cells (MSCs), which are inherently refractory to transfection. Existing vectors have limitations: PEI is cytotoxic and linear poly(L-lysine) (L-PLL) has poor transfection efficiency. Transfection efficiency (pGFP, day 7)…
Read the article →Journal of Controlled Release2018ResearchNon-viral Gene Delivery
Brynn R. Olden, Yilong Cheng, Jonathan L. Yu, Suzie H. Pun
CAR T cell immunotherapy requires efficient ex vivo gene delivery to primary human T cells, but viral vectors have limitations including cost, cargo size, insertional mutagenesis risk, and manufacturing complexity. Non-viral cationic polymers are attractive alternatives but historically show low gene transfer…
Read the article →ACS Applied Bio Materials (Just Accepted Manuscript)2018ResearchNon-viral Gene Delivery
Chao Wang, Pengfei Sun, Gaina Wang, Pengcheng Yuan, Rongcui Jiang, Wenjun Wang, Wei Huang, Quli Fan
Dendritic cell (DC)-based vaccines require efficient antigen delivery, but free ovalbumin (OVA) is poorly taken up by DCs and is often degraded, sequestered, or exocytosed. Existing OVA delivery systems often suffer from low loading capacity (<10%), lack of imaging ability, or chemical modification that can impair…
Read the article →Journal of Visualized Experiments (JoVE)2018ResearchNon-viral Gene Delivery
Elana Ben-Akiva, Kelly R. Rhodes, Randall A. Meyer, Jordan J. Green
Artificial antigen-presenting cells (aAPCs) are promising for immune modulation, and anisotropic (ellipsoidal) particles have shown improved T-cell stimulation over spherical particles. However, widely used methods for generating anisotropic particles, such as thin-film stretching, can be difficult to implement…
Read the article →International Journal of Pharmaceutics2018ResearchNon-viral Gene Delivery
Haimanti Mandal, Sameer S. Katiyar, Rajan Swami, Varun Kushwah, Parmeshwar B. Katare, Anand Kumar Meka, Sanjay K. Banerjee, Amirali Popat, Sanyog Jain
Non-viral gene delivery vectors are safer than viral vectors but often suffer from lower transfection efficiency and cytotoxicity. ε-Poly-L-lysine (ε-PLL) is a naturally occurring, FDA GRAS cationic polymer with low molecular weight and potential for low toxicity, but its use as a pDNA nanocarrier for efficient in…
Read the article →Colloids and Surfaces B: Biointerfaces2018ResearchDrug Delivery
Amirhossein Bahreyni, Mona Alibolandi, Mohammad Ramezani, Atefeh Sarafan Sadeghi, Khalil Abnous, Seyed Mohammad Taghdisi
Conventional chemotherapy for breast and colon cancers suffers from low specificity, rapid drug clearance, and severe toxic side effects on healthy tissues, while chemoresistance and metastasis remain major causes of cancer-related mortality. There is an unmet need for targeted delivery systems that can co-deliver…
Read the article →Advanced Healthcare Materials (Adv. Healthcare Mater.)2018ResearchNon-viral Gene Delivery
Sungjin Min, Yoonhee Jin, Chen Yuan Hou, Jayoung Kim, Jordan J. Green, Taek Jin Kang, Seung-Woo Cho
Current cancer treatments (chemotherapy, radiotherapy) suffer from a lack of selectivity for tumour cells, causing severe side effects and therapeutic resistance. While gene therapy is a promising alternative, viral vectors pose safety risks (immunogenicity, tumorigenicity), and nonviral vectors often suffer from low…
Read the article →Biomacromolecules2018ResearchDrug Delivery
Jayoung Kim, James G. Shamul, Sagar R Shah, Alyssa Shin, Ben J Lee, Alfredo Quiñones‐hinojosa, Jordan J. Green
Many anticancer small molecules have poor aqueous solubility, and verteporfin (VP) has mainly been used as a photodynamic therapy agent, which carries photosensitivity and delivery limitations. PBAE-based materials have been developed extensively for nucleic acid delivery but are less explored for non-genetic…
Read the article →Nature Communications2017ResearchNon-viral Gene Delivery
H.F. Moffett, M.E. Coon, S. Radtke, S.B. Stephan, L. Mcknight, A. Lambert, B.L. Stoddard, H.P. Kiem, M.T. Stephan
Therapies based on genetically engineered immune cells (CAR T cells, HSCs) are transforming medicine, but the viral and electroporation methods used to create these cytoreagents are complex, expensive, and time-consuming. There is a growing need for transient "hit-and-run" genetic programming (transcription factors…
Read the article →PLOS ONE2017ResearchNon-viral Gene Delivery
Susanne Przybylski, Michaela Gasch, Anne Marschner, Marcus Ebert, Alexander Ewe, Gisa Helmig, Nadja Hilger, Stephan Fricke, Susanne Rudzok, Achim Aigner, Jana Burkhardt
Nanoparticle-based gene delivery methods are promising for transfecting immune cells, but their impact on basic immune functions such as proliferation—a cornerstone of cellular immunity—has not been systematically investigated. Understanding whether transfection reagents non-specifically influence immune cell…
Read the article →Nature Nanotechnology2017ResearchNon-viral Gene Delivery
Tyrel T. Smith, Sirkka B. Stephan, Howell F. Moffett, Laura E. Mcknight, Weihang Ji, Diana Reiman, Emmy Bonagofski, Martin E. Wohlfahrt, Smitha P. S. Pillai, Matthias T. Stephan
Adoptive T cell therapy with CAR-engineered T cells has shown impressive clinical results, but the ex vivo manufacturing process is complex, expensive, and requires specialised facilities, limiting widespread application. A method to programme circulating T cells directly in vivo with tumour-recognising capabilities…
Read the article →Theranostics2017ResearchNon-viral Gene Delivery
Xi Zhu, Wei Tao, Danny Liu, Jun Wu, Zilei Guo, Xiaoyuan Ji, Zameer Bharwani, Lili Zhao, Xiaoping Zhao, Omid C. Farokhzad, Jinjun Shi
Surface PEGylation of nanoparticles (NPs) improves circulation time and tumour accumulation but also hinders intracellular delivery, creating the "PEG dilemma" for siRNA therapeutics. While stimuli-responsive de-PEGylation strategies exist, they add complexity to NP design and synthesis. A tunable, serum…
Read the article →Nature Communications2017ResearchNon-viral Gene Delivery
Daniela Schmid, Chun Gwon Park, Christina A. Hartl, Nikita Subedi, Adam N. Cartwright, Regina Bou Puerto, Yiran Zheng, James Maiarana, Gordon J. Freeman, Kai W. Wucherpfennig, Darrell J. Irvine, Michael S. Goldberg
Systemic immune stimulation for cancer immunotherapy is associated with autoimmune-type pathologies, as the doses required to break immune tolerance can invoke undesired host-vs.-host effects. Targeting endogenous immune cell subsets in the circulation—which actively migrate into tumours—could concentrate…
Read the article →2017ResearchNon-viral Gene Delivery
Petra Furedi, Zsofia Edit Papay, Kristof Kovacs, Borbala Dalmadi Kiss, Krisztina Ludanyi, Istvan Antal, Imre Klebovich
Topical fungal infections, including ocular mycoses, are increasing, and voriconazole (VCZ) is an effective antifungal but has poor water solubility, limiting liquid ophthalmic formulations. Lipid-based nanoparticles (LNPs/SLNs) may improve VCZ solubility, loading, and topical delivery. Optimised formulation (SLN2)…
Read the article →Colloids and Surfaces B: Biointerfaces2017ResearchNon-viral Gene Delivery
Pinnapireddy Sr, Duse L, Strehlow B, Schäfer J, Bakowsky U
Polyethylenimine (PEI)-based gene delivery is limited by cytotoxicity, rapid degradation, and low cellular uptake. A safer, more stable non-viral system was needed for both gene delivery and gene knockdown. Physicochemical properties: DDC liposomes ~198.7 nm, ζ = −30.9 mV; IPEI polyplexes ~166.2 nm, ζ = +19.1 mV…
Read the article →Biomaterials2017ResearchNon-viral Gene Delivery
Yoshizaki Y, Yuba E, Sakaguchi N, Koiwai K, Harada A, Kono K
Efficient cancer vaccine carriers need both antigen delivery to dendritic cells (DCs) and DC activation. Previous pH-sensitive polymer-modified liposomes delivered antigen to DC cytosol but had limited adjuvant potency, and combining cationic lipid TRX with MPLA reduced antitumor effects, suggesting a need for…
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