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
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
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)
Review
Pharmacology & Pharmacy
Antoine Hakim, Benjamin Guido, Lokesh Narsineni, Ding-Wen Chen, Marianna Foldvari
Summary: Glaucoma is a progressive disease caused by the death of retinal ganglion cells and axonal loss in the optic nerve. Elevated intraocular pressure is a major risk factor contributing to this condition. Current management mainly focuses on lowering intraocular pressure, but it does not address optic nerve degeneration. Gene therapy, especially non-viral delivery systems, shows promise in controlling genes involved in glaucoma pathophysiology and providing neuroprotection.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
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)
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)
Review
Environmental Sciences
Qi Lu
Summary: The use of nanomaterials in cancer therapy can address the limitations of conventional therapies by utilizing nanotechnology to overcome chemoresistance, radio-resistance, and lack of specific tumor targeting. Cyclodextrins (CDs) are amphiphilic cyclic oligosaccharides that can be synthesized from natural sources and have shown increasing potential in improving solubility and bioavailability of bioactive compounds and therapeutics for cancer treatment. CDs are widely used in drug and gene delivery for cancer therapy, improving anti-proliferative and anticancer effects through targeted delivery and enhanced accumulation at the tumor site.
ENVIRONMENTAL RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Maria L. Ibba, Giuseppe Ciccone, Carla L. Esposito, Silvia Catuogno, Paloma H. Giangrande
Summary: Messenger RNA (mRNA) holds great potential as therapeutics for various human pathologies, but the key to its clinical translation lies in the development of safe and effective delivery strategies. Non-viral delivery systems, although slightly less efficacious compared to viral systems, offer important advantages in terms of biosafety and versatility. Challenges and future applications of mRNA therapeutics are also discussed in this review.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Review
Pharmacology & Pharmacy
Maria L. Santana-Armas, C. Tros de Ilarduya
Summary: Gene therapy is an emerging strategy for cancer treatment, and modifying non-viral vectors can enhance safety and efficiency. Structural modifications, addition of specific ligands, and other methods can improve the specificity and gene delivery efficiency of non-viral vectors.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Review
Biotechnology & Applied Microbiology
Sepideh Jahangiri, Maedeh Rahimnejad, Narges Nasrollahi Boroujeni, Zarrin Ahmadi, Puria Motamed Fath, Sepideh Ahmadi, Moein Safarkhani, Navid Rabiee
Summary: The overall success in launching discovered drugs is restricted by the high rate of late-stage failures. Reliable methods are needed to predict the effectiveness and toxicity of medicines early in the drug development process. Modern in vitro disease models and advanced technology, such as 3D bioprinting, can be used to expedite drug discovery. 3D bioprinting has the potential to revolutionize pharmaceutical studies and improve gene delivery and tissue engineering.
JOURNAL OF GENE MEDICINE
(2022)
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
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
Biochemistry & Molecular Biology
Myriam Sainz-Ramos, Idoia Gallego, Ilia Villate-Beitia, Jon Zarate, Ivan Maldonado, Gustavo Puras, Jose Luis Pedraz
Summary: This review highlights the critical importance of efficient delivery of genetic material into cells for translating gene therapy into clinical practice, with a focus on non-viral vector systems as a promising alternative to virus-based gene delivery. The challenges and potential strategies for clinical application of non-viral vectors in mainstream medicine, including efficiency, biocompatibility, and long-lasting effect, are discussed in order to promote safe and efficient non-viral gene delivery systems for clinical applications in the gene therapy field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Teng Huang, Jia Gao, Long Cai, Hao Xie, Yuhan Wang, Yi Wang, Qing Zhou
Summary: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with a high mortality rate. The commercially available pharmaceuticals show some effects but more effective therapeutics are urgently needed. Gene therapy, using non-viral vectors, is a promising strategy for the treatment of IPF. The non-viral vectors, such as liposomes, polymers, and proteins/peptides, are highlighted for their low immunogenicity and good biocompatibility.
Letter
Pharmacology & Pharmacy
Mitsuru Hashida
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Multidisciplinary Sciences
Ryosaku Ota, Kanako So, Masahiro Tsuda, Yuriko Higuchi, Fumiyoshi Yamashita
Summary: The paper presents a method for predicting HIV drug resistance using genotypes, utilizing techniques such as homology modeling and Bayesian conditional mutual information theory to handle incomplete sequencing data, proposing a way to effectively incorporate uncertain information into the modeling process.
Article
Multidisciplinary Sciences
Yoshihisa Tanaka, Kako Higashihara, Mai Adachi Nakazawa, Fumiyoshi Yamashita, Yoshinori Tamada, Yasushi Okuno
Summary: Researchers used Bayesian networks to analyze gene regulatory networks in response to SARS-CoV-2, revealing dynamic changes from interferon signaling to inflammatory cytokine signaling cascades. They successfully captured a COVID-19 patient-specific network and explored local regulatory systems influenced by SARS-CoV-2 in host cells.
SCIENTIFIC REPORTS
(2021)
Article
Materials Science, Biomaterials
Sayaka Deguchi, Masahiro Tsuda, Kaori Kosugi, Ayaka Sakamoto, Natsumi Mimura, Ryosuke Negoro, Emi Sano, Takuro Nobe, Kazuya Maeda, Hiroyuki Kusuhara, Hiroyuki Mizuguchi, Fumiyoshi Yamashita, Yu-suke Torisawa, Kazuo Takayama
Summary: The study evaluated drug absorption to the PDMS device and investigated the drug responsiveness of human hepatocytes cultured in the PDMS device. The absorption rates of different compounds to the PDMS device were measured and found to be correlated with their octanol/water distribution coefficient values. Furthermore, the hepatocyte-chips were used to examine the response to drugs typically used to evaluate hepatic functions.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2021)
Article
Chemistry, Multidisciplinary
Emi Sano, Sayaka Deguchi, Naoki Matsuoka, Masahiro Tsuda, Mengyang Wang, Kaori Kosugi, Chihiro Mori, Keisuke Yagi, Aya Wada, Shinsuke Yamasaki, Tsuyoshi Kawai, Masahide Yodogawa, Hiroyuki Mizuguchi, Norihito Nakazawa, Fumiyoshi Yamashita, Yu-suke Torisawa, Kazuo Takayama
Summary: The study investigated the feasibility of using a FEPM-based hepatocyte chip with lower drug absorption for drug discovery research. The FEPM-based chip showed higher detection of drug metabolites and lower hepatocyte cytotoxicity compared to the PDMS-based chip, indicating its potential utility in drug metabolism and toxicity studies.
Article
Pharmacology & Pharmacy
Mohammad Karim Haidar, Fumiyoshi Yamashita, Mitsuru Hashida
Summary: Regardless of the PLGA type with different lactic/glycolic acid ratios, microspheres prepared via the solid-in-oil-in-water (S/O/W) method showed a much higher encapsulation efficiency (EE) and faster drug release compared to microspheres prepared via the co-solvent method. Preparation methods, pH of the aqueous phase, and volume of the aqueous phase were the most influencing parameters on the EE. Confirmation experiment results indicated a 5.76 db increase in signal-to-noise ratio from the initial condition. Minocycline release was fastest with PLGA (50:50) microspheres, followed by PLGA (75:25) and PLGA (85:15).
TURKISH JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Physiology
Nagomi Kurebayashi, Takashi Murayama, Ryosaku Ota, Junji Suzuki, Kazunori Kanemaru, Takuya Kobayashi, Seiko Ohno, Minoru Horie, Masamitsu Iino, Fumiyoshi Yamashita, Takashi Sakurai
Summary: Type 2 ryanodine receptor (RYR2) is a cardiac Ca2+ release channel that is associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). This study demonstrates that CPVT mutations lower the threshold [Ca-2(+)](ER) for spontaneous Ca-2(+) release by enhancing the [Ca-2(+)](cyt)-dependent activity of RYR2, without modulating the [Ca-2(+)](ER) sensitivity of RYR2.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Chanikarn Chantarasrivong, Ryu Okada, Yuuki Yamane, Xue Yang, Yuriko Higuchi, Miku Konishi, Naoko Komura, Hiromune Ando, Ryuji Yokokawa, Fumiyoshi Yamashita
Summary: Tumor spheroids with a perfusable vascular network were constructed to evaluate drug delivery systems targeting tumor vasculature. The results suggest that 3'-CE sLeX mimic liposomes are a promising carrier for targeting tumor vasculature, and proinflammatory cytokine treatment may be beneficial in pharmacokinetic studies.
DRUG METABOLISM AND PHARMACOKINETICS
(2022)
Article
Pharmacology & Pharmacy
Mengyang Wang, Masahiro Tsuda, Sayaka Deguchi, Yuriko Higuchi, Kanako So, Yu-suke Torisawa, Kazuo Takayama, Fumiyoshi Yamashita
Summary: Recently, liver-on-a-chip models have gained increasing attention for pharmacokinetics and toxicity screenings. Researchers have found that perfluoropolyether (PFPE) elastomer, a chemically repellent material, could be an alternative to the commonly used polydimethylsiloxane (PDMS) material in microfluidic devices. The PFPE devices showed improved cell performance with increased production of albumin and urea, as well as enhanced metabolic activity of hepatocytes under dynamic flow conditions compared to static conditions. Although PFPE devices still exhibited some sorption, they demonstrated better chemical repellency and may provide better performance in ADMET evaluation than PDMS devices.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Chemistry, Analytical
Ryohei Ueno, Masahiro Kuninori, Takumi Sumi, Ramin Banan Sadeghian, Yuji Takata, Azusa Iguchi, Masahiro Tsuda, Fumiyoshi Yamashita, Kentaro Ichikawa, Ryuji Yokokawa
Summary: Microphysiological systems (MPS) are emerging as a technology for next-generation non-clinical drug screening. These microfluidic devices mimic the physiological functions of human organs and have the potential to reduce animal experiments, improve drug efficacy prediction, and lower drug discovery costs.
Article
Pharmacology & Pharmacy
Shoko Nomura, Erike W. Sukowati, Yuko Shigeno, Maiko Takahashi, Akari Kato, Yoshimi Benno, Fumiyoshi Yamashita, Hidefumi Mukai
Summary: We demonstrate the potential use of Blautia coccoides JCM1395(T) as a tumor-targeted live bacterial therapeutic. We developed a reliable quantitative analysis method for bacterial detection in biological tissues, overcoming the hindrance caused by the thick outer layer of peptidoglycans in Gram-positive bacteria. Using this method, we individually detected Blautia coccoides JCM1395(T) and Bacteroides vulgatus JCM5826(T) in tumors of mice receiving intravenous mixture injection. This simple and reproducible method, without genetic modification, can be applied to explore a wide range of bacterial species.
Article
Chemistry, Multidisciplinary
Ryosaku Ota, Fumiyoshi Yamashita
Summary: This review discusses the current status and challenges of applying machine-learning techniques to the analysis and prediction of pharmacokinetic data. While traditional mathematical models have limitations in explaining ADME processes and predicting pharmacokinetic time profiles, machine learning offers a data-driven approach for handling complex phenomena. Machine-learning models generally outperform linear models and new structures, such as transfer learning and generative adversarial networks, are continuously being proposed. The key issue now is how to apply these emerging machine-learning technologies to the field of pharmacokinetics/pharmacodynamics.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Pharmacology & Pharmacy
Yuko Sasaki, Hirotaka Tatsuoka, Masahiro Tsuda, Takumi Sumi, Yuka Eguchi, Kanako So, Yuriko Higuchi, Kazuo Takayama, Yusuke Torisawa, Fumiyoshi Yamashita
Summary: Microfluidic devices are a promising tool for studying drug transport and metabolism. This study investigated drug transport across Caco-2 cell layers in microfluidic devices and found that drug lipophilicity influenced permeability. Fluidic conditions also promoted drug metabolism. These findings provide valuable information for the application of microfluidic devices in drug research.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2022)
Article
Toxicology
Qiyue Zhang, Shiori Taniguchi, Kanako So, Masahiro Tsuda, Yuriko Higuchi, Mitsuru Hashida, Fumiyoshi Yamashita
Summary: Drug-induced liver injury (DILI) is a major cause of drug development failure and post-approval withdrawal. This study identified CREB as a potential sensitive biomarker for DILI prediction and suggested that its response to stress induced by high-risk drugs might be primarily regulated by the PKA/CREB signaling pathway.
JOURNAL OF TOXICOLOGICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Yukinobu Kodama, Ayako Tokunaga, Junya Hashizume, Hiroo Nakagawa, Hitomi Harasawa, Tomoaki Kurosaki, Tadahiro Nakamura, Koyo Nishida, Mikiro Nakashima, Mitsuru Hashida, Shigeru Kawakami, Hitoshi Sasaki
Summary: A biocompatible splenic vector for a DNA vaccine against melanoma was developed, showing strong luciferase activity and suppression of melanoma growth and metastasis in mice. The ternary complex mainly transfected into macrophages in the spleen, indicating its suitability for DNA vaccination. The ternary complex also exhibited low acute and liver toxicities in mice, confirming its safety profile.
