Review
Oncology
Junsheng Li, Wen Wang, Jia Wang, Yong Cao, Shuo Wang, Jizong Zhao
Summary: Gene therapy using viral vectors to deliver therapeutic genes for specific antitumor effects is a promising approach for treating GBM, offering potential applications in the future.
FRONTIERS IN ONCOLOGY
(2021)
Article
Engineering, Biomedical
Meirong Li, Zheng-Ian Lin, Jingyu Yang, Haoqiang Huang, Guan-Lin Liu, Qiqi Liu, Xinmeng Zhang, Ying Zhang, Zhourui Xu, Haoming Lin, Yujuan Chai, Xin Chen, Bao-Tsan Ko, Jia Liu, Chih-Kuang Chen, Chengbin Yang
Summary: Osteosarcoma is a highly invasive and deadly cancer that often occurs in children and adolescents. The overexpression of PLK1 gene in tumors promotes cancer cell proliferation and transformation, making it a therapeutic target for osteosarcoma. However, current RNA interference-based therapies lack a safe and efficient nonviral gene vector. In this study, biodegradable and CO2-derivative cationic poly(vinylcyclohexene carbonates) (CPCHCs) were used as gene vectors for siPLK1 therapeutic strategy in osteosarcoma treatment. Among them, CPCHC60 showed excellent performance in gene transfection efficiency, endo-lysosome escaping, biodegradability, and biosafety. The treatment with CPCHCs/siRNA nanoparticles significantly down-regulated the expression level of PLK1 gene in osteosarcoma cells, leading to cell arrest and apoptosis, resulting in significant tumor regression both in vitro and in vivo. This study provides new insights into the development of superior nonviral gene vectors for cancer treatment and holds high potential for translational nanomedicine applications.
ADVANCED HEALTHCARE MATERIALS
(2023)
Review
Biochemistry & Molecular Biology
Liangnan Tong, Danqing Liu, Zhiyue Cao, Nannan Zheng, Chenchen Mao, Shujuan Liu, Liangcan He, Shaoqin Liu
Summary: Gene therapy using siRNA has gained much attention for its unique mechanism of action, non-toxicity, and good tolerance, allowing for targeted killing of cancer cells without harming healthy tissues. Compared to traditional treatments, siRNA therapy has fewer side effects and can provide long-term and even curative effects. It has also shown promise in the treatment of cardiovascular diseases, gastrointestinal diseases, and hepatitis B.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, Research & Experimental
Sepideh Mirzaei, Mahmood Khaksary Mahabady, Amirhossein Zabolian, Alireza Abbaspour, Peyman Fallahzadeh, Maedeh Noori, Farid Hashemi, Kiavash Hushmandi, Salman Daneshi, Alan Prem Kumar, Amir Reza Aref, Saeed Samarghandian, Pooyan Makvandi, Haroon Khan, Michael R. Hamblin, Milad Ashrafizadeh, Ali Zarrabi
Summary: GBM is a serious brain tumor with no cure, requiring new genetic approaches for treatment. The use of siRNA can target and silence genes responsible for disease progression in GBM cells.
Article
Pharmacology & Pharmacy
Asma Ghaemi, Masoume Vakili-Azghandi, Khalil Abnous, Seyed Mohammad Taghdisi, Mohammad Ramezani, Mona Alibolandi
Summary: Gene therapy has the potential to prevent or treat various genetic or acquired diseases by regulating gene and protein expression. Effective delivery systems are needed to ensure successful gene therapy, and oral delivery approaches show promise in treating diseases such as inflammatory bowel disease and cancer. This review provides an update on the development of oral gene delivery techniques for gene therapy and vaccination purposes.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Medicine, Research & Experimental
Cynthia D. Anderson, Jennifer Ataam Arthur, Yuan Zhang, Nike Bharucha, Ioannis Karakikes, Ralph V. Shohet
Summary: CRISPR-Cas9-based genome editing technologies have the potential for clinical translation, but delivering nucleic acids into target cells in vivo is challenging. This study presents a new method using focused ultrasound targeted microbubble destruction to deliver CRISPR-Cas9 base editing vectors to the mouse liver. The results demonstrate successful base editing in mouse liver cells, but with lower specificity and more off-target base exchange in vivo.
MOLECULAR THERAPY NUCLEIC ACIDS
(2023)
Review
Biochemistry & Molecular Biology
Adriana Aurelia Chis, Carmen Maximiliana Dobrea, Luca-Liviu Rus, Adina Frum, Claudiu Morgovan, Anca Butuca, Maria Totan, Anca Maria Juncan, Felicia Gabriela Gligor, Anca Maria Arseniu
Summary: Gene-directed enzyme prodrug therapy (GDEPT) is a promising strategy for prodrug delivery, with benefits including enhanced efficacy and reduced off-target toxicity. Non-viral vectors, such as dendrimers, have gained interest due to their decreased immunogenicity and high specificity for delivering genes in GDEPT therapy.
Review
Chemistry, Multidisciplinary
Shuai Qu, Renfa Liu, Nisi Zhang, Yunxue Xu, Xiuli Yue, Zhifei Dai
Summary: This article reviews the recent advances in targeted non-viral nucleic acid delivery for gene therapy of atherosclerosis, including hepatocyte-targeted delivery and delivery to different cells within the plaques.
Review
Engineering, Biomedical
Jiayu Gu, Zhourui Xu, Qiqi Liu, Shiqi Tang, Wenguang Zhang, Shouxia Xie, Xiaoyan Chen, Jiajie Chen, Ken-Tye Yong, Chengbin Yang, Gaixia Xu
Summary: In recent years, messenger RNA (mRNA) vaccines have shown great potential as replacements for conventional vaccines due to their low risk of mutagenesis, safety and effectiveness, rapid and scalable production, and low-cost manufacturing. Non-viral mRNA vectors are considered ideal choices for future clinical translation due to their safety, sufficient packaging capability, low immunogenicity, and versatility. This review focuses on the recent progress in the development of non-viral mRNA vectors, including lipid nanoparticles, polymers, peptides, and exosomes. It also discusses the latest advances in clinical trials of mRNA vaccines, as well as the current challenges and future possibilities for the clinical translation of these vectors.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Engineering, Biomedical
Yu Wang, Yan Tang, Xiao-mei Zhao, Gui Huang, Jin-hong Gong, Shu-di Yang, Hui Li, Wen-jun Wan, Chang-hao Jia, Gang Chen, Xue-nong Zhang
Summary: In this study, a multifunctional non-viral vector was constructed for efficient delivery of CRISPR/Cas9 plasmid. The vector actively targeted tumor cells and delivered the cargo into cell nuclei, resulting in genome editing effects. By disrupting the MTH1 gene, the growth of non-small cell lung cancer was inhibited, promoting cell apoptosis in tumor tissue and reducing liver metastasis.
ACTA BIOMATERIALIA
(2022)
Article
Chemistry, Organic
Michela Lomazzi, Valentina Franceschi, Valentina Bagnacani, Carlo Alberto Vezzoni, Gaetano Donofrio, Alessandro Casnati, Francesco Sansone
Summary: The tetra-L-arginino-tetrahexyloxycalix[4]arene 1 has shown remarkable abilities to compact and deliver various types of nucleic acid cargos into cells. Small structural changes in the calixarene vectors may affect their ability to compact DNA and deliver cargo into cells.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Biotechnology & Applied Microbiology
Chenfei Wang, Chaolan Pan, Haiyang Yong, Feifei Wang, Tao Bo, Yitong Zhao, Bin Ma, Wei He, Ming Li
Summary: Gene therapy holds great promise for treating a wide range of genetic diseases by delivering functional genes into targeted cells or tissues. However, the lack of safe and efficient gene delivery vehicles remains a major obstacle to its clinical implementation. This review comprehensively outlines the novel non-viral gene delivery vectors with potential applications in gene therapy.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Yi Yan, Xiao-Yu Liu, An Lu, Xiang-Yu Wang, Lin-Xia Jiang, Jian-Cheng Wang
Summary: RNA-based therapy is a promising strategy for disease treatment, and recent advances in non-viral delivery systems have shown potential in protecting RNA, facilitating cell internalization, and controlled release of therapeutics.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Pharmacology & Pharmacy
Ellen S. Hauck, James G. Hecker
Summary: Lipid-mediated nucleic acid delivery is an important alternative method for gene therapy, providing rapid, high payload and low risk delivery. However, delivering nucleic acids to the central nervous system faces challenges of cell diversity and blood brain barrier limitations.
Article
Pharmacology & Pharmacy
Anastasios Nalbadis, Marie-Luise Trutschel, Henrike Lucas, Jana Luetzkendorf, Annette Meister, Karsten Maeder
Summary: Local controlled release of siRNA is achieved by evaluating three different non-viral siRNA carriers, with DL suspension found to be the most suitable for providing 60 days of controlled release. Fluorescence imaging is an effective tool for measuring siRNA release, as validated by comparison with HPLC data. Further testing shows that the released siRNA possesses effective controlled release properties.
Article
Chemistry, Multidisciplinary
So-Jung Gwak, Jeoung Soo Lee
Review
Biochemistry & Molecular Biology
Shoaib Iqbal, Mark Blenner, Angela Alexander-Bryant, Jessica Larsen
Article
Computer Science, Interdisciplinary Applications
Sarah Mbiki, Jerome McClendon, Angela Alexander-Bryant, Jordon Gilmore
MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING
(2020)
Article
Nanoscience & Nanotechnology
Emily M. Miller, Timothy M. Samec, Angela A. Alexander-Bryant
Summary: Ovarian cancer, characterized by lack of early symptoms and accurate diagnosis, poses the most lethal threat to women. Treatment complexity increases upon recurrence due to drug resistance development. Research in targeted nanoparticle delivery systems aims to improve specificity and efficacy in therapies for drug-resistant ovarian cancer.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2021)
Article
Engineering, Biomedical
Da Un Jeong, Sooneon Bae, Christian Macks, Joseph Whitaker, Michael Lynn, Ken Webb, Jeoung Soo Lee
Summary: Incorporation of dexamethasone-conjugated hyaluronic acid (HA-DXM) into a hydrolytically degradable, photo-cross-linkable poly (ethylene) glycol-bis-(acryloyloxy acetate) (PEG-bis-AA) hydrogel showed significant reductions in cavity size, inflammatory response, and apoptosis in a controlled cortical impact (CCI) rat traumatic brain injury (TBI) model. Animals treated with PEG-bis-AA/HA-DXM hydrogel exhibited higher neuronal cell survival and improved motor functional recovery compared to control groups receiving PEG-bis-AA/HA and no treatment.
BIOMEDICAL MATERIALS
(2021)
Review
Biotechnology & Applied Microbiology
Jun Gao, Minkyung Khang, Zhen Liao, Megan Detloff, Jeoung Soo Lee
Summary: This review highlights recent achievements in nanomaterial-based therapy for spinal cord injury, specifically targeting blood-spinal cord barrier disruption, mitigation of the inflammatory response, and alleviation of oxidative stress, providing promising therapeutic strategies for secondary SCI research.
Article
Biotechnology & Applied Microbiology
Joshua Woo, Jeoung Soo Lee
Summary: The study showed that Lyo. PgP/pGFP polyplexes prepared with 5% sucrose as a lyoprotectant remained stable for up to 6 months and retained transfection efficiency for up to 4 months. This indicates that polyplexes based on Lyo. PgP retain bioactivity during extended storage, potentially facilitating transport to remote regions and less stable settings for gene therapy.
Article
Polymer Science
Mohamed F. Attia, Ahmed S. Montaser, Md Arifuzzaman, Megan Pitz, Khouloud Jlassi, Angela Alexander-Bryant, Stephen S. Kelly, Frank Alexis, Daniel C. Whitehead
Summary: In this study, electrospun cellulose acetate nanofibers loaded with a non-steroidal anti-inflammatory drug and coated with poly(acrylamide) hydrogel polymer were developed and characterized. The presence of the poly-AAm hydrogel polymer significantly affected the release kinetics of the drug, promoting a more consistent release rate compared to non-coated nanofibers. The coated nanofibers showed significantly higher drug release concentrations compared to non-coated nanofibers, and overall demonstrated excellent cytocompatibility.
Review
Biochemistry & Molecular Biology
Megan E. Pitz, Alexandra M. Nukovic, Margaret A. Elpers, Angela A. Alexander-Bryant
Summary: Self-assembling peptides are versatile, tunable, and biocompatible vectors for therapeutic cargo delivery. Accurate prediction of their secondary and supramolecular structures is crucial for peptide design, although current computational modeling falls short in this aspect. Analyzing patterns in literature and the relationship between structures, sequences, and applications can guide informed peptide design.
MACROMOLECULAR BIOSCIENCE
(2022)
Article
Biotechnology & Applied Microbiology
Christian Macks, Daun Jeong, Jeoung Soo Lee
Summary: In this study, a nanocarrier PgP was developed for the delivery of Rm and its therapeutic efficacy on secondary injury and motor function in a TBI model was evaluated. The results showed that Rm-PgP restored cAMP level, reduced lesion volume and neuroinflammation, and improved motor function. This suggests the potential of a single injection of Rm-PgP for acute mild TBI treatment.
Article
Engineering, Biomedical
Timothy Samec, Jessica Boulos, Serena Gilmore, Anthony Hazelton, Angela Alexander-Bryant
Summary: This review discusses the application of peptide-based delivery systems in cancer therapeutics. Peptide systems can alleviate systemic side effects caused by current delivery strategies and enhance therapeutic delivery and cancer targetability.
MATERIALS TODAY BIO
(2022)
Article
Biochemistry & Molecular Biology
Christian Macks, Daun Jeong, Sooneon Bae, Ken Webb, Jeoung Soo Lee
Summary: Dexamethasone-loaded hydrogels can reduce neuroinflammation, apoptosis, and lesion volume, as well as improve neuronal cell survival and motor function recovery in a rat mild-TBI model, making it a promising therapeutic intervention for TBI treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Timothy Samec, Kharimat Lora Alatise, Jessica Boulos, Serena Gilmore, Anthony Hazelton, Angela Alexander-Bryant
Summary: The survival rate of advanced-stage ovarian cancer patients has shown little improvement over the past decade. Current treatment strategies have been largely ineffective in treating advanced disease, leading to systemic toxicity and drug-resistant metastatic cancer. This study evaluates the potential of novel fusogenic peptide carriers to deliver short interfering RNA (siRNA) targeting casein kinase II (CSNK2A1) for reducing the aggressiveness of ovarian cancer. The results demonstrate the ability of these peptide variants to effectively deliver bioactive siRNAs to ovarian cancer cells, leading to a significant knockdown of CSNK2A1 expression, decreased cell migration and recolonization, and reduced tumor growth and migration.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)