Article
Biochemistry & Molecular Biology
Dmytro Honcharenko, Cristina S. J. Rocha, Karin E. Lundin, Jyotirmoy Maity, Stefan Milton, Ulf Tedebark, Merita Murtola, Malgorzata Honcharenko, Andis Slaitas, C. I. Edvard Smith, Rula Zain, Roger Stromberg
Summary: This study synthesized 2'-O-AECM-modified ONs and found that these modified ONs have efficient splice-switching activity even without inclusion of PS linkages. Furthermore, partial inclusion of PS linkages does not significantly reduce the splice-switching efficacy. In addition, conjugation of 2'-O-AECM ONs with an endosomal escape peptide increases splice-switching activity.
NUCLEIC ACID THERAPEUTICS
(2022)
Article
Physiology
Yoshitsugu Aoki, Cristina S. J. Rocha, Taavi Lehto, Shouta Miyatake, Henrik Johansson, Yasumasa Hashimoto, Joel Z. Nordin, Imre Mager, Misako Aoki, McClorey Graham, Chaitra Sathyaprakash, Thomas C. Roberts, Matthew J. A. Wood, Mark A. Behlke, Samir El Andaloussi
Summary: This study demonstrates that the inclusion of PS increases nuclear delivery and splice switching of 2OMe in various cell lineages, including muscle, neuronal, liver, and bone cells. Modulation of 2OMePS-binding proteins may enhance SSO delivery efficacy.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Florian Malard, Cameron D. Mackereth, Sebastien Campagne
Summary: This article discusses the early stage of spliceosome assembly in eukaryotes, focusing on the factors that influence U1 snRNP's selection of splice sites in pre-mRNA. It also includes examples of diseases that affect this selection and recent therapeutic advances.
Article
Multidisciplinary Sciences
Michael W. Baughn, Ze'ev Melamed, Jone Lopez-Erauskin, Melinda S. Beccari, Karen Ling, Aamir Zuberi, Maximilliano Presa, Elena Gonzalo-Gil, Roy Maimon, Sonia Vazquez-Sanchez, Som Chaturvedi, Mariana Bravo-Hernandez, Vanessa Taupin, Stephen Moore, Jonathan W. Artates, Eitan Acks, I. Sandra Ndayambaje, Ana R. Agra de Almeida Quadros, Paayman Jafar-Nejad, Frank Rigo, C. Frank Bennett, Cathleen Lutz, Clotilde Lagier-Tourenne, Don W. Cleveland
Summary: Loss of nuclear TDP-43 is a key factor in neurodegeneration. The mislocalization of TDP-43 leads to cryptic splicing and polyadenylation of pre-mRNAs encoding stathmin-2. Targeting dCasRx or ASOs can suppress cryptic splicing, restoring axonal regeneration and stathmin-2-dependent lysosome trafficking.
Article
Endocrinology & Metabolism
Maria V. Luna Velez, Omar Paulino da Silva Filho, Gerald W. Verhaegh, Onno van Hooij, Najoua El Boujnouni, Roland Brock, Jack A. Schalken
Summary: This study evaluates the efficacy of cell-penetrating peptide-mediated delivery system for antisense oligonucleotides in castration-resistant prostate cancer cell line models and identifies the optimal formulation conditions for efficient uptake.
Article
Biochemistry & Molecular Biology
Loren L. Flynn, Chalermchai Mitrpant, Abbie Adams, Ianthe L. Pitout, Anja Stirnweiss, Sue Fletcher, Steve D. Wilton
Summary: The use of antisense oligonucleotides in disease treatment is expanding, with improvements in chemistry enhancing their stability and effectiveness. Rational sequence design and chemistry optimization are crucial for ensuring antisense activity.
Article
Biochemistry & Molecular Biology
Atsuki Nakagami, Qiyue Mao, Geraldine Gouhier, Hidetoshi Arima, Hiroaki Kitagishi
Summary: A highly specific host-guest system capable of functioning in living cells was demonstrated in this study. Fluorescence resonance energy transfer (FRET) phenomenon between the host-guest pair was observed in living cells using confocal microscopy techniques, indicating the stability of the supramolecular complex within the cells. The bio-orthogonality of the host-guest pair in living cells was confirmed through a series of experiments.
Article
Pharmacology & Pharmacy
Mert Oktem, Enrico Mastrobattista, Olivier G. de Jong
Summary: The study investigates the use of LAH5 peptide for delivering CRISPR-Cas9 components into target cells. The results show successful cellular uptake and cargo delivery, as well as gene editing and repair in various cell lines.
Review
Biotechnology & Applied Microbiology
Muthusamy Ramakrishnan, K. Shanmugha Rajan, Sileesh Mullasseri, Sarin Palakkal, Krishnan Kalpana, Anket Sharma, Mingbing Zhou, Kunnummal Kurungara Vinod, Subbiah Ramasamy, Qiang Wei
Summary: There is growing evidence that post-transcriptional RNA modifications can greatly impact crop production. However, the roles of the abundant RNA modifications of pseudouridine and 2'-O-methylation in plants remain unclear. This review discusses the latest methods and insights gained in mapping these modifications in plants, as well as the limitations in current high-throughput technologies. Future challenges in regulating the plant epitranscriptome are also highlighted.
PLANT BIOTECHNOLOGY JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Niklas Freund, Alexander Taylor, Sebastian Arangundy-Franklin, Nithya Subramanian, Sew-Yeu Peak-Chew, Amy M. Whitaker, Bret D. Freudenthal, Mikhail Abramov, Piet Herdewijn, Philipp Holliger
Summary: In this study, a two-residue "gate" was discovered in an archaeal DNA polymerase, which enables the synthesis of 2'-modified RNA oligomers. This discovery expands the application potential of 2'-modified RNA in nucleic acid therapeutics and biotechnology.
Article
Engineering, Chemical
Fang Xie, Yuan Fang, Xin Liu, Xin Cong, Yangchao Luo, Jiaojiao Zhou, Zia-ud Din, Shuiyuan Cheng, Jie Cai
Summary: This study successfully prepared O/W/O and W/O/W emulsions using a simple method. These emulsions have important applications in healthy food development, as they can efficiently load selenium-enriched peptides and vitamin E, and exhibit good antioxidant properties. Additionally, they effectively mask the odor of selenium-enriched peptides.
JOURNAL OF FOOD ENGINEERING
(2024)
Article
Chemistry, Multidisciplinary
Virginia Martin-Nieves, Luis Miguel Menendez-Mendez, Carme Fabrega, Susana Fernandez, Yogesh S. Sanghvi, Miguel Ferrero, Ramon Eritja
Summary: Nucleosides and their analogues, especially l-nucleosides, are important molecules with potential antiviral and antiproliferative activity. They have emerged as a new class of therapeutic agents due to their comparable biological activity, improved toxicological properties, and greater metabolic stability compared to d-nucleosides. l-nucleosides can also be used as building blocks for l-oligonucleotides, which have similar physical properties as d-oligonucleotides but are resistant to nuclease degradation, non-toxic, and immunologically passive. The synthesis and incorporation of 2'-O-methyl/2'-O-MOE-l-nucleoside pyrimidine derivatives into G-rich oligonucleotides were described, showing their potential in providing enhanced nuclease resistance without significant impact on nucleic acid structural properties.
Article
Medicine, Research & Experimental
Nan Zhang, Jing Li, Wenxia Gao, Wangwei Zhu, Jianqin Yan, Ziyun He, Li Li, Fang Wu, Yuji Pu, Bin He
Summary: Lipid polymer nanocomplexes can serve as efficient drug carriers for chemo-immunotherapy of cancer. This study demonstrates their ability to efficiently internalize into cancer cells, induce immunogenic cell death, and block PD-L1, thus achieving antitumor effects.
MOLECULAR PHARMACEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Jennifer Porat, Viktor A. Slat, Stephen D. Rader, Mark A. Bayfield
Summary: Splicing requires tight coordination between dynamic spliceosomal RNAs and proteins. In this study, the authors found that Bmc1 and Pof8 play important roles in the formation of a distinct U6 snRNP that promotes U6 2'-O-methylation, and identified a non-canonical snoRNA guiding this methylation. They also discovered that the 5' γ-monomethyl phosphate capping activity of Bmc1 is not required for its role in promoting snoRNA-guided 2'-O-methylation. These findings provide insights into the novel functions of Bmc1/MePCE family members and the general role of Bmc1 and Pof8 in guiding noncoding RNP assembly.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Anna S. Pavlova, Kristina I. Yakovleva, Anna V. Epanchitseva, Maxim S. Kupryushkin, Inna A. Pyshnaya, Dmitrii V. Pyshnyi, Elena I. Ryabchikova, Ilya S. Dovydenko
Summary: The study showed that siRNA modified with the phosphoryl guanidine (PG) group exhibited increased resistance to RNase A but decreased thermodynamic stability. However, PG-modified siRNA retained its activity when the modifications were introduced into the passenger strand.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Maxime Gestin, Henrik Helmfors, Luca Falato, Nicola Lorenzon, Filip Ilias Michalakis, Ulo Langel
Article
Biochemistry & Molecular Biology
Nicola Lorenzon, Maxime Gestin, Ulo Langel
Summary: This study developed a peptide through protein mimicry to activate the dopamine 1 receptor signaling pathway inside cells, potentially serving as a peptide-based treatment for Parkinson's disease.
INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS
(2021)
Article
Biochemical Research Methods
Yafeng Zhu, Lukas M. Orre, Yan Zhou Tran, Georgios Mermelekas, Henrik J. Johansson, Alina Malyutina, Simon Anders, Janne Lehtio
MOLECULAR & CELLULAR PROTEOMICS
(2020)
Article
Biochemical Research Methods
Yan Zhou Tran, Rezan Minozada, Xiaofang Cao, Henrik J. Johansson, Rui M. Branca, Brinton Seashore-Ludlow, Lukas M. Orre
MOLECULAR & CELLULAR PROTEOMICS
(2020)
Article
Chemistry, Applied
Hani Nasser Abdelhamid, Moataz Dowaidar, Ulo Langel
MICROPOROUS AND MESOPOROUS MATERIALS
(2020)
Article
Chemistry, Applied
Hani Nasser Abdelhamid, Moataz Dowaidar, Mattias Hallbrink, Ulo Langel
MICROPOROUS AND MESOPOROUS MATERIALS
(2020)
Article
Biology
Andra Brunner, Aldwin Suryo Rahmanto, Henrik Johansson, Marcela Franco, Johanna Viiliainen, Mohiuddin Gazi, Oliver Frings, Erik Fredlund, Charles Spruck, Janne Lehtio, Juha K. Rantala, Lars-Gunnar Larsson, Olle Sangfelt
Article
Biotechnology & Applied Microbiology
Maria Lytrivi, Kassem Ghaddar, Miguel Lopes, Victoria Rosengren, Anthony Piron, Xiaoyan Yi, Henrik Johansson, Janne Lehtio, Mariana Igoillo-Esteve, Daniel A. Cunha, Lorella Marselli, Piero Marchetti, Henrik Ortsater, Decio L. Eizirik, Miriam Cnop
Article
Biochemical Research Methods
Tirsa L. E. van Westering, Henrik J. Johansson, Britt Hanson, Anna M. L. Coenen-Stass, Yulia Lomonosova, Jun Tanihata, Norio Motohashi, Toshifumi Yokota, Shin'ichi Takeda, Janne Lehtio, Matthew J. A. Wood, Samir EL Andaloussi, Yoshitsugu Aoki, Thomas C. Roberts
MOLECULAR & CELLULAR PROTEOMICS
(2020)
Article
Biochemistry & Molecular Biology
Heesoo Jeong, Yan Yu, Henrik J. Johansson, Frank C. Schroeder, Janne Lehtio, Nathaniel M. Vacanti
Summary: Stable-isotope tracing is a method used to measure intracellular metabolic pathway utilization by feeding a cell system a stable-isotope-labeled tracer nutrient. An algorithm and tool, PolyMID-Correct, have been developed to computationally remove the influence of naturally occurring heavy isotopes, making the method more accurate and reliable. This algorithm is applicable to data collected on both low- and high-mass resolution mass spectrometers, and PolyMID-Correct is open source under an MIT license.
Article
Multidisciplinary Sciences
Katalin Erdelyi, Tamas Ditroi, Henrik J. Johansson, Agnes Czikora, Noemi Balog, Laxmi Silwal-Pandit, Tomoaki Ida, Judit Olasz, Dorottya Hajdu, Zoltan Matrai, Orsolya Csuka, Koji Uchida, Jozsef Tovari, Olav Engebraten, Takaaki Akaike, Anne-Lise Borresen Dale, Miklos Kasler, Janne Lehtio, Peter Nagy
Summary: Basal like breast cancer (BLBC) is an aggressive subtype of breast tumors with high Cys demand and reprogrammed Cys metabolism. CBS overexpression promotes tumor progression in BLBC, while CBS silencing makes BLBC cells more vulnerable to oxidative stress and CySSCy deprivation, leading to ferroptosis. This study suggests that persulfide-producing pathways are potential therapeutic targets for BLBC.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Physiology
Yoshitsugu Aoki, Cristina S. J. Rocha, Taavi Lehto, Shouta Miyatake, Henrik Johansson, Yasumasa Hashimoto, Joel Z. Nordin, Imre Mager, Misako Aoki, McClorey Graham, Chaitra Sathyaprakash, Thomas C. Roberts, Matthew J. A. Wood, Mark A. Behlke, Samir El Andaloussi
Summary: This study demonstrates that the inclusion of PS increases nuclear delivery and splice switching of 2OMe in various cell lineages, including muscle, neuronal, liver, and bone cells. Modulation of 2OMePS-binding proteins may enhance SSO delivery efficacy.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Oncology
Janne Lehtio, Taner Arslan, Ioannis Siavelis, Yanbo Pan, Fabio Socciarelli, Olena Berkovska, Husen M. Umer, Georgios Mermelekas, Mohammad Pirmoradian, Mats Jonsson, Hans Brunnstrom, Odd Terje Brustugun, Krishna Pinganksha Purohit, Richard Cunningham, Hassan Foroughi Asl, Sofi Isaksson, Elsa Arbajian, Mattias Aine, Anna Karlsson, Marija Kotevskaz, Carsten Gram Hansen, Vilde Drageset Haakensen, Aslaug Helland, David Tamborero, Henrik J. Johansson, Rui M. Branca, Maria Planckz, Johan Staaf, Lukas M. Orre
Summary: Researchers conducted a proteogenomic analysis of non-small cell lung cancer, identifying molecular subtypes with distinct immune-evasion mechanisms and therapeutic targets. They validated their classification method in separate clinical cohorts, discovering high neoantigen burden linked to global hypomethylation and immune evasion mechanisms associated with STK11 mutation-dependent HNF1A activation and FGL1 expression. Furthermore, they developed a data-independent acquisition mass-spectrometry-based NSCLC subtype classification method, validating it in independent cohorts and demonstrating clinical utility.
Meeting Abstract
Oncology
Andra Brunner, Henrik Johansson, Alexandros Kourtesakis, Juha Rantala, Charles Spruck, James Wohlschlegel, Janne Lehtio, Olle Sangfelt
Article
Multidisciplinary Sciences
Ganna Oliynyk, Maria Victoria Ruiz-Perez, Lourdes Sainero-Alcolado, Johanna Dzieran, Hanna Zirath, Hector Gallart-Ayala, Craig E. Wheelock, Henrik J. Johansson, Roland Nilsson, Janne Lehtio, Marie Arsenian-Henriksson
Review
Chemistry, Multidisciplinary
Zhiyuan Shi, Yong Hu, Xin Li
Summary: Controlled drug delivery systems that can respond to mechanical force offer a unique solution for on-demand drug activation and release. Among various mechanical stimuli, ultrasound (US) has advantages in achieving spatiotemporally controlled drug release. Traditional US-triggered drug release relies on heat-induced phase transitions or chemical transformations, while the cutting-edge approach of Sonopharmacology leverages polymer mechanochemistry. The remaining challenges and potential future directions in this field are also discussed.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Lijie Zheng, Yuanzheng Chen, Xun Gu, Yingying Li, Hanqing Zhao, Wenjun Shao, Tao Ma, Chuanbin Wu, Qingqing Wang
Summary: In this study, a novel dosage form consisting of dissolving microneedles and an adhesive transdermal patch was developed for the treatment of rheumatoid arthritis. In vitro and in vivo experiments demonstrated that the combination of drugs delivered by this dosage form effectively reduced joint inflammation and damage.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Kyungjik Yang, Hwa Seung Han, Seung Hwan An, Kyung Hoon Park, Keonwook Nam, Shinha Hwang, Yuyeon Lee, Sung Yeon Cho, Taehyung Kim, Deokyeong Choe, Sang Won Kim, Wonkyu Yu, Hyunah Lee, Jiyong Park, Sangguan You, Dong- Gyu Jo, Ki Young Choi, Young Hoon Roh, Jae Hyung Park
Summary: This study developed CP-loaded CS microcapsules to enhance the oral bioavailability of CP through controlled gastrointestinal delivery. The optimized microcapsules exhibited desirable physicochemical properties, showed anti-photoaging effects via antioxidant activity, and achieved controlled release in the gastrointestinal tract. This research provides a simple and economical approach for enhancing the oral bioavailability of CP for customized bioactive compound administration.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Huiyang Li, Shuo Liu, Wenjin Dai, Bingmei Yao, Yong Zhou, Sujia Si, Hairong Yu, Riguang Zhao, Fang Jin, Liqun Jiang
Summary: Changes in bodily fluid pressures are crucial in diseases like high-altitude pulmonary edema (HAPE). Researchers have developed hydrostatic pressure-sensitive multivesicular liposomes (PSMVLs) that can release drugs in response to pressure changes, with potential applications in HAPE treatment. Animal experiments showed that this system provides better protection for lung tissues and respiratory function, reducing the occurrence of pulmonary edema.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Qian Hu, Hongbing Lan, Yinmei Tian, Xiaonan Li, Mengmeng Wang, Jiao Zhang, Yulin Yu, Wei Chen, Li Kong, Yuanyuan Guo, Zhiping Zhang
Summary: Coacervate droplets formed through liquid-liquid phase separation have potential as delivery vesicles for therapeutics. However, their lack of physiological stability and membranes are challenges. In this study, polylysine-polynucleotide complex coacervate droplets with favorable stability were formulated to concentrate molecules and nanoparticles. Phospholipid membranes were further coated on the droplets to create coacervate-based artificial protocells (ArtPC) with membrane-like structures. These biofunctional ArtPC effectively reduced blood uric acid levels and prevented renal injuries.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Xiaowei Wang, Hongwei Lu, Fang Luo, Dan Wang, Apeng Wang, Xuelei Wang, Wenkai Feng, Xiaobo Wang, Jiayi Su, Mingliang Liu, Guimin Xia
Summary: Four novel lipid-like GEM diesters were synthesized and encapsulated into liposomes to improve the antitumor efficacy of Gemcitabine. The liposomes loaded with dimyristoyl GEM (LipodmGEM) showed enhanced cellular uptake, improved inhibition of cell migration, and a greatly extended half-life compared to free Gemcitabine. LipodmGEM successfully enriched the drug in the tumor and exhibited excellent anticancer efficacy in vivo with negligible systemic toxicity.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Pengyu Li, Jieyi Pan, Yating Dong, Yingying Sun, Yalong Wang, Kang Liao, Yili Chen, Xin Deng, Shihui Yu, Haiyan Hu
Summary: Chronic pulmonary infection caused by Pseudomonas aeruginosa is a serious public health problem with high mortality rates. In this study, infection-microenvironment responsive nanoparticles were developed to eradicate biofilms and inhibit virulence. These nanoparticles showed promising results in treating chronic pulmonary infections.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Yajing Sun, Ze Lu, John A. Taylor, Jessie L. S. Au
Summary: A recent development in cancer chemotherapy is the use of cytotoxics to induce tumor-specific immune response through immunogenic cell death (ICD). This study describes a method that utilizes immunostaining and machine-learning to identify cells with ecto-CRT in intact 3-dimensional tissues. The method was successfully applied to study drug-induced ICD in human bladder cancer.
JOURNAL OF CONTROLLED RELEASE
(2024)
Review
Chemistry, Multidisciplinary
Rafat Ali, Shantanu Sen, Rohil Hameed, Aamir Nazir, Sandeep Verma
Summary: This review provides a focused overview of emerging strategies for delivering gasotransmitters in a controlled and sustained manner to reestablish neurophysiological homeostasis.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Jing Chen, Xinyi Zhang, Jinshen Zhang, Zhaoxia Wang, Guilan Zhu, Ming Geng, Jinmiao Zhu, Yajun Chen, Wei Wang, Youcui Xu
Summary: In this study, a multifunctional responsive hydrogel system was developed for synergistic reoxygenation and chemo/photothermal therapy. The hydrogel system showed both therapeutic effects against metastatic breast cancer and wound infection, making it a promising strategy for treating and preventing tumor recurrence and associated wound infection.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Baoshan Huang, Na Zhang, Xinying Qiu, Rui Zeng, Shuimiao Wang, Mengxia Hua, Qing Li, Kaihui Nan, Sen Lin
Summary: This study revealed that robust ROS can oxidize mitochondrial DNA (ox-mtDNA) and cause its release into the cytosol, resulting in the activation of NLRP3 inflammasome. By using the mitochondria-targeted antioxidant SkQ1 and a novel mitochondria-targeted nanoparticle (SkQ1 NP), it was found that mitochondrial ROS scavenging could in situ inhibit DED-induced mtDNA oxidation and suppress NLRP3-mediated inflammation.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Wenqi Liu, Cheng Hu, Linyu Long, Shuyi He, Wen Zhang, Zhicun Wang, Li Yang, Yunbing Wang
Summary: Myocardial infarction is the leading cause of cardiovascular mortality, and current treatment methods have limitations. This study developed a smart carrier that can release different therapeutic substances for different pathological processes, effectively improving cardiac function, promoting cardiac repair, and preventing ventricular remodeling.
JOURNAL OF CONTROLLED RELEASE
(2024)