Article
Biotechnology & Applied Microbiology
Yifei Wang, Chunxi Wang, Justin Sylvers, Tatiana Segura, Fan Yuan
Summary: Electrotransfection (ET) is a non-viral approach used for delivering nucleic acids, but its efficiency is often low in vivo. In this study, we developed nanoenhancers that diffuse slowly in tissues and are poorly absorbed by blood and lymph microvessels. These nanoenhancers were found to enhance ET efficiency both in vitro and in vivo, and their mechanism of action was related to the inhibition of lysosomal functions.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Matej Kranjc, Janja Dermol-Cerne, Tjasa Potocnik, Vitalij Novickij, Damijan Miklavcic
Summary: This study demonstrates the feasibility of using high-intensity pulsed electromagnetic field (HI-PEMF) for non-viral delivery of genetic material in vitro. The results show that HI-PEMF can cause DNA adsorption to the cell membrane and induce gene electrotransfection. Endocytosis is also identified as a possible mechanism for introducing large molecules into cells by HI-PEMF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yifei Wang, Chun-Chi Chang, Fan Yuan
Summary: Electrotransfection is a non-viral method to deliver nucleic acids into cells. This study determined the minimal copy number of plasmid DNA (pDNA) per cell required for transgene expression and developed a statistical framework to predict pDNA copy number in the nucleus. A novel approach was developed to obtain isolated nuclei with minimal contamination by extranuclear pDNA, enabling accurate measurement of intranuclear pDNA. The data showed that the copy number of pDNA per nucleus depended on cell culture period and pDNA dose for electrotransfection, and were used to improve the understanding of pDNA transport kinetics in cells.
BIOELECTROCHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Ruta Palepsiene, Martynas Maciulevicius, Paulius Ruzgys, Baltramiejus Jakstys, Saulius Satkauskas
Summary: Gene electrotransfer (GET) is a promising technique for gene therapy, but its success rate is influenced by the understanding of electroporation mechanism and other factors. This study analyzed the impact of low concentrations of Ca2+ on DNA electrotransfer and found that even 0.25 mM CaCl2 can significantly decrease the efficiency of GET and cell viability. The observed decrease in pDNA electrotransfer was not due to cell death but secondary mechanisms. The findings highlight the importance of Ca2+ in gene electrotransfer and its potential application in vivo.
APPLIED SCIENCES-BASEL
(2023)
Article
Oncology
Kevin Hollevoet, Debby Thomas, Griet Compernolle, Giles Vermeire, Elien De Smidt, Stephanie De Vleeschauwer, Trevor R. F. Smith, Paul D. Fisher, Maarten Dewilde, Nick Geukens, Paul Declerck
Summary: DNA-encoded delivery and in vivo expression of antibody therapeutics offer an innovative approach for cancer treatment. In this study, sheep were used as animal models to evaluate the delivery protocol and the impact of pDNA dose and host immune response on the pharmacokinetics of the expressed antibody. The results showed robust and prolonged production of anti-cancer DNA-encoded antibody therapeutics in sheep, providing valuable insights for clinical translation.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Divya Sharma, Sanjay Arora, Jagdish Singh, Buddhadev Layek
Summary: Gene therapy aims to transfer genetic materials into targeted cells for disease treatment or prevention. Nonviral vectors have gained attention for their safety, payload capacity, and stealth abilities, but face challenges in overcoming intracellular and extracellular barriers. This review highlights current advancements in nonviral gene delivery systems and their future potential.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Chemistry, Multidisciplinary
Wenliang Wang, Aaron Tasset, Ilya Pyatnitskiy, Peter Lin, Arjun Bellamkonda, Rohan Mehta, Christian Gabbert, Feng Yuan, Heba Galaa Mohamed, Nicholas A. Peppas, Huiliang Wang
Summary: This study presents a two-stage condensation approach for efficient nuclear transport of DNA in nonviral gene delivery. The approach involves cross-linking DNA plasmids to form bundled DNA, and packaging the bundled DNA into cationic vectors. The results show improved gene transfection efficiency both in vitro and in vivo.
Article
Biochemistry & Molecular Biology
Anna Bulysheva, Loree Heller, Michael Francis, Frency Varghese, Carly Boye, Richard Heller
Summary: A novel monopolar electroporation system and methodologies were developed for in vivo electroporation, showing enhanced gene expression through targeted electroporation and gene transfer achieved by an asymmetric anode/cathode electrode applicator geometry.
BIOELECTROCHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Yujie Yang, Zhen Liu, Hongchao Ma, Meiwen Cao
Summary: Gene therapy provides new strategies for treating diseases by modifying abnormal genes, and peptide-based vectors are promising tools for efficient gene delivery. This review discusses the design and application of peptide-based nonviral gene vectors, their role in overcoming biological barriers, and the current challenges and future prospects for the development of such vectors.
Article
Biochemistry & Molecular Biology
Reginald M. Atkins, Timothy J. Fawcett, Richard Gilbert, Andrew M. Hoff, Richard Connolly, Douglas W. Brown, Mark J. Jaroszeski
Summary: The research in this publication was primarily supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and in part by the National Institute of Biomedical Imaging and Bioengineering. Additional support was provided by various departments at USF, with approximately 80% of the study costs financed with federal money.
BIOELECTROCHEMISTRY
(2021)
Review
Oncology
Argyrios Gyftopoulos, Ioannis A. Ziogas, Andrew S. Barbas, Dimitrios Moris
Summary: IRE, as a local ablative technique used in conjunction with chemotherapy, has shown increased overall survival in patients with locally advanced pancreatic cancer by possibly enhancing the action and delivery of chemotherapeutic drugs. Investigating the potentiating mechanism of IRE on immunotherapy, oncolytic virus, and dendritic cell treatments is of great importance for improving current treatment algorithms for pancreatic cancer in the future.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemical Research Methods
Marco Bassetto, Merve Sen, Florent Poulhes, Blanca Arango-Gonzalez, Elise Bonvin, Cedric Sapet, Marius Ueffing, Olivier Zelphati
Summary: The prevalence of retinal disorders causing visual impairment and blindness is on the rise globally, but effective treatment options remain scarce. The development of pharmacological and molecular therapies is hindered by challenges in drug delivery to the back of the eye. A novel method using magnetic nanoparticles (MNPs) has been developed to efficiently deliver siRNA throughout all layers of the rat retina, offering a promising strategy for RNAi-based molecular and gene therapy in retinal disorders.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Dipeng Zhao, Jian Qin, Jie An, Hao Zhang, Junling Li, Hejie Wang, Rong Du, Yongming He
Summary: Electroporation is a non-viral mediated transfection technique that offers advantages such as being harmless, easy to operate, and less expensive. However, there is a need for further improvement in electroporation efficiency, as there is no universal standard electrotransfection step for different cell types, and inappropriate parameters can result in low transfection efficiency and high cell mortality.
MOLECULAR BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Jiaxuan Chen, Dandan Zhu, Baoping Lian, Kangjie Shi, Peng Chen, Ying Li, Wenyi Lin, Ling Ding, Qiulin Long, Yang Wang, Erik Laurini, Wenjun Lan, Yun Li, Aura Tintaru, Caoyun Ju, Can Zhang, Sabrina Pricl, Juan Iovanna, Xiaoxuan Liu, Ling Peng
Summary: Nucleic acid therapeutics serve as an important drug modality for targeting undruggable targets, responding to evolving pathogens, and precision medicine at the gene level. Dendrimers, as precision delivery systems, have been utilized for selective and on-demand delivery of DNA and siRNA. The properties and performance of these dendrimers were systematically studied, and they exhibited cargo-adaptive and selective delivery, tumor targeting, and redox-responsive cargo release. The dendrimers outperformed currently available vectors in tumor and cancer cell-specific delivery of siRNA and DNA therapeutics in various cancer models. This study provides a pathway for engineering tailor-made vectors for nucleic acid delivery and precision medicine.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Engineering, Biomedical
Sarah Y. Neshat, Chun Hei Ryan Chan, Jawaun Harris, Osamah M. Zmily, Savannah Est-Witte, Johan Karlsson, Sydney R. Shannon, Manav Jain, Joshua C. Doloff, Jordan J. Green, Stephany Y. Tzeng
Summary: Immuno-oncology therapies aim to induce sustained tumor regression, but current methods are in need of improvement. An antigen-free method of cancer immunotherapy that stimulates the immune system without knowledge of neoantigens has been developed, along with a local delivery system to minimize systemic toxicity. A gene delivery nanoparticle platform has been engineered to reprogram the tumor microenvironment and activate cytotoxic lymphocytes, resulting in tumor regression and clearance.
Article
Medicine, Research & Experimental
Lisa D. Cervia, Chun-Chi Chang, Liangli Wang, Mao Mao, Fan Yuan
MOLECULAR THERAPY-NUCLEIC ACIDS
(2018)
Article
Anesthesiology
Lisa D. Cervia, Joseph P. McGowan, Allyson J. Weseley
Article
Multidisciplinary Sciences
Lisa D. Cervia, Chun-Chi Chang, Liangli Wang, Fan Yuan
Article
Oncology
Jianguo Huang, Mohit Sachdeva, Eric Xu, Timothy J. Robinson, Lixia Luo, Yan Ma, Nerissa T. Williams, Omar Lopez, Lisa D. Cervia, Fan Yuan, Xiaodi Qin, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Tomoyo Okada, Samuel Singer, Irene L. Andrulis, Jay S. Wunder, Alexander J. Lazar, Brian P. Rubin, Krista Pipho, Stephano S. Mello, Jimena Giudice, David G. Kirsch
MOLECULAR CANCER RESEARCH
(2020)
Article
Oncology
Chunxi Wang, Chun-Chi Chang, Liangli Wang, Fan Yuan
Article
Biochemistry & Molecular Biology
Liangli Wang, Chun-Chi Chang, Justin Sylvers, Fan Yuan
Summary: Plasmid DNA is commonly used for non-viral gene delivery, but only a fraction of molecules function as transcription templates in the nucleus. Researchers developed a statistical framework to establish the minimal amount of pDNA molecules needed for transgene expression. Experimental data under different conditions could be quantitatively explained or predicted using this framework.
BIOELECTROCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yifei Wang, Chun-Chi Chang, Fan Yuan
Summary: Electrotransfection is a non-viral method to deliver nucleic acids into cells. This study determined the minimal copy number of plasmid DNA (pDNA) per cell required for transgene expression and developed a statistical framework to predict pDNA copy number in the nucleus. A novel approach was developed to obtain isolated nuclei with minimal contamination by extranuclear pDNA, enabling accurate measurement of intranuclear pDNA. The data showed that the copy number of pDNA per nucleus depended on cell culture period and pDNA dose for electrotransfection, and were used to improve the understanding of pDNA transport kinetics in cells.
BIOELECTROCHEMISTRY
(2023)
Article
Cell & Tissue Engineering
Justin Sylvers, Yifei Wang, Fan Yuan
Summary: This study investigated the relative importance of passive and active pathways for plasmid DNA (pDNA) nuclear entry and subsequent gene expression. The research revealed that cell cycle arrest decreased diffuse pDNA and increased punctate pDNA, resulting in a decrease in total intranuclear pDNA. The cell cycle arrest also increased reporter mRNA synthesis but had no substantial impact on reporter protein expression. These findings will contribute to future studies on nonviral gene delivery mechanisms.
CELLULAR AND MOLECULAR BIOENGINEERING
(2023)
Article
Materials Science, Biomaterials
Mao Mao, Chun-Chi Chang, Adrian Pickar-Oliver, Lisa D. Cervia, Liangli Wang, Jing Ji, Paloma B. Liton, Charles A. Gersbach, Fan Yuan
ADVANCED BIOSYSTEMS
(2020)
Meeting Abstract
Biophysics
Lisa D. Cervia, Chun-Chi Chang, Liangli Wang, Fan Yuan
BIOPHYSICAL JOURNAL
(2017)
