Article
Chemistry, Multidisciplinary
Yu Wang, Shuting Chen, Jingyi Zhang, Qing Ye, Yin Liu
Summary: DNA nanomaterials, as a novel type of nanomaterials, have great potential in biomedical applications due to their high precision, controllability, and biocompatibility. Therapeutic drugs based on DNA nanomaterials have shown beneficial effects on various diseases. However, the instability of DNA nanomaterials greatly hinders their clinical application. In this study, we designed and synthesized a stable topological DNA nanostructure, DNA Nano Trihedron (DNT), which could enter MCF-7 cells without a transfection agent. DNT induced significant changes in gene expression and exhibited significant inhibitory effects on MCF-7 cells. Even after two months of storage, DNT still retained its inhibitory effect on MCF-7 cells.
Article
Biochemistry & Molecular Biology
Remko Goossens, Nisha Verwey, Yavuz Ariyurek, Fred Schnell, Annemieke Aartsma-Rus
Summary: The study reveals that the non-sequential splicing of DMD transcript and the retention time of adjacent introns have an impact on the efficiency of AON. Targeting an out-of-frame exon flanked by a "slow" intron at its 5'-end leads to higher exon skipping efficiency. Furthermore, placing AON closer to the 5'-end of the target exon results in better skipping efficiency regardless of the splicing speed of adjacent introns.
Article
Pharmacology & Pharmacy
Sarah J. Overby, Estefania Cerro-Herreros, Jorge Espinosa-Espinosa, Irene Gonzalez-Martinez, Nerea Moreno, Juan M. Fernandez-Costa, Jordina Balaguer-Trias, Javier Ramon-Azcon, Manuel Perez-Alonso, Thorleif Moller, Beatriz Llamusi, Ruben Artero
Summary: The study demonstrates the therapeutic effects of using blockmiR antisense technology to increase MBNL protein in DM1 cells and mice. By blocking the binding sites of specific microRNAs, the mis-splicing, subcellular localization, and gene expression associated with Myotonic Dystrophy Type 1 can be rescued.
Editorial Material
Genetics & Heredity
Muhammad Riaz Khan, Raymund J. Wellinger, Benoit Laurent
Summary: Long noncoding RNA (lncRNA) genes, like protein-coding genes, consist of introns and exons and undergo constitutive and/or alternative splicing after transcription. This review outlines the current understanding of lncRNA splice variants and their functional implications in cell biology.
TRENDS IN GENETICS
(2021)
Article
Clinical Neurology
Saija Ahonen, Silvia Nitschke, Tamar R. Grossman, Holly Kordasiewicz, Peixiang Wang, Xiaochu Zhao, Dikran R. Guisso, Sahba Kasiri, Felix Nitschke, Berge A. Minassian
Summary: Lafora disease is a fatal progressive myoclonus epilepsy caused by the accumulation of long branches in glycogen molecules leading to the formation of Lafora bodies. In mouse models, targeting the GYS1 mRNA with an antisense oligonucleotide (Gys1-ASO) prevented the formation of Lafora bodies and halted disease progression, showing promise as a potential therapy for this catastrophic epilepsy.
Article
Chemistry, Multidisciplinary
Ze-Kun Wang, Jia-Le Lin, Yun-Chang Zhang, Chen-Wu Yang, Ya-Kun Zhao, Zheng-Wei Leng, Hui Wang, Dan-Wei Zhang, Jiang Zhu, Zhan-Ting Li
Summary: Five water-soluble flexible organic frameworks were synthesized by quantitatively forming a hydrazone bond in water, displaying tunable diameters and low cytotoxicity. These frameworks can quickly include and deliver DNA into cells, with a delivery rate of up to 99.5%.
MATERIALS CHEMISTRY FRONTIERS
(2021)
Article
Pharmacology & Pharmacy
Mohadeseh Dastpeyman, Ramin Sharifi, Azin Amin, John A. Karas, Brittany Cuic, Yijun Pan, Joseph A. Nicolazzo, Bradley J. Turner, Fazel Shabanpoor
Summary: This study demonstrates that integrating endosomal escape domains with CPPs can improve the intracellular delivery efficiency of ASOs, and enhance the efficiency of BBB-permeability and CNS activity of systemically administered ASOs.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Review
Clinical Neurology
Nika Maani, Sophie Karolczak, James J. Dowling
Summary: The field of genetic therapies is rapidly advancing, with the first gene-based treatments now in clinical practice. While there are currently no approved drug therapies for congenital myopathies, several candidate therapeutics, including gene replacement therapy and antisense oligonucleotide-based gene knockdown, are in development. Genetic therapies are bringing precision medicine to neurological diseases, with congenital myopathies being ideally suited for these approaches.
CURRENT OPINION IN NEUROLOGY
(2021)
Article
Cell Biology
Julio C. Corral-Serrano, Paul E. Sladen, Daniele Ottaviani, Olivia F. Rezek, Dimitra Athanasiou, Katarina Jovanovic, Jacqueline van der Spuy, Brian C. Mansfield, Michael E. Cheetham
Summary: This study demonstrates the potential therapeutic effect of eupatilin on CEP290-associated retinal diseases. Eupatilin improves cilia formation and length, reduces rhodopsin retention, and modulates gene expression in retinal organoids.
Article
Biochemistry & Molecular Biology
Karima Relizani, Lucia Echevarria, Faouzi Zarrouki, Cecile Gastaldi, Chloe Dambrune, Philippine Aupy, Adrian Haeberli, Marek Komisarski, Thomas Tensorer, Thibaut Larcher, Fedor Svinartchouk, Cyrille Vaillend, Luis Garcia, Aurelie Goyenvalle
Summary: Tricyclo-DNA (tcDNA) is a promising oligonucleotide analog with therapeutic potential, especially when conjugated with palmitic acid for improved delivery to muscle tissues. This conjugation enhances the potency of tcDNA-ASO, resulting in functional improvement in dystrophic mice with significantly reduced dose, while also showing a promising safety profile for clinical development in neuromuscular diseases.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Clinical Neurology
Gemma L. Carvill, Tyler Matheny, Jay Hesselberth, Scott Demarest
Summary: This review summarizes the pathogenic mechanisms underlying monogenic epilepsies and discusses the potential of novel precision therapeutics in treating these disorders. Understanding the pathogenic mechanisms of each genetic epilepsy is crucial for designing precision therapies that are likely to benefit patients. Novel therapeutics discussed include gene therapy, gene editing, antisense oligonucleotides, and protein replacement, with examples from the literature illustrating and reinforcing the discussions.
Article
Multidisciplinary Sciences
Taiki Tsurusaki, Kazuki Sato, Hiroki Imai, Kunihiro Hirai, Daisuke Takahashi, Takeshi Wada
Summary: Phosphorodiamidate morpholino oligonucleotides (PMOs) are a promising type of antisense oligonucleotides, but their challenging synthesis makes them difficult to access. This research presents an efficient synthetic approach for PMOs using the H-phosphonate approach. The use of phosphonium-type condensing reagents significantly reduced coupling times compared with the current synthetic approach. This approach would facilitate the large-scale synthesis of PMOs and accelerate their popularity and accessibility as a next-generation therapy.
SCIENTIFIC REPORTS
(2023)
Review
Genetics & Heredity
Ying-Xuan Xie, Wen-Qi Lv, Yi-Kun Chen, Shunyan Hong, Xiang-Ping Yao, Wan-Jin Chen, Miao Zhao
Summary: Neurogenetic diseases are neurological conditions with a genetic cause that are mostly incurable. Gene therapy approaches such as viral vectors delivery, antisense oligonucleotides, and gene editing have shown promising therapeutic effects in treating neurogenetic diseases.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Review
Clinical Neurology
Sonia Messina, Maria Sframeli, Lorenzo Maggi, Adele D'Amico, Claudio Bruno, Giacomo Comi, Eugenio Mercuri
Summary: Spinal muscular atrophy (SMA) is a severe disorder of motor neurons, but with three available therapeutic options now, ethical, medical, and financial issues have been raised. Each therapeutic strategy has its weaknesses and strengths, and clinicians need to understand them to optimize clinical care.
NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Alexandra Litvinchuk, Tien-Phat Huynh, Yang Shi, Rosemary J. Jackson, Mary B. Finn, Melissa Manis, Caroline M. Francis, Ainsley C. Tran, Patrick M. Sullivan, Jason D. Ulrich, Bradley T. Hyman, Tracy Cole, David M. Holtzman
Summary: Therapeutic reduction of ApoE4 levels through ASO treatment showed significant protective effects on tau pathology, neurodegeneration, neuroinflammation, and synaptic density, indicating a potential therapeutic approach for APOE4 carriers with tauopathy, including Alzheimer's disease.
ANNALS OF NEUROLOGY
(2021)
Article
Genetics & Heredity
Danielle G. M. Bosch, Frouke N. Boonstra, Rolph Pfundt, Frans P. M. Cremers, Bert B. A. de Vries
CLINICAL DYSMORPHOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Lonneke Haer-Wigman, Hadas Newman, Rina Leibu, Nathalie M. Bax, Hagit N. Baris, Leah Rizel, Eyal Banin, Amir Massarweh, Susanne Roosing, Dirk J. Lefeber, Marijke N. Zonneveld-Vrieling, Ofer Isakov, Noam Shomron, Dror Sharon, Anneke I. Den Hollander, Carel B. Hoyng, Frans P. M. Cremers, Tamar Ben-Yosef
HUMAN MOLECULAR GENETICS
(2015)
Article
Genetics & Heredity
Susanne Kohl, Ditta Zobor, Wei-Chieh Chiang, Nicole Weisschuh, Jennifer Staller, Irene Gonzalez Menendez, Stanley Chang, Susanne C. Beck, Marina Garcia Garrido, Vithiyanjali Sothilingam, Mathias W. Seeliger, Franco Stanzial, Francesco Benedicenti, Francesca Inzana, Elise Heon, Ajoy Vincent, Jill Beis, Tim M. Strom, Guenther Rudolph, Susanne Roosing, Anneke I. den Hollander, Frans P. M. Cremers, Irma Lopez, Huanan Ren, Anthony T. Moore, Andrew R. Webster, Michel Michaelides, Robert K. Koenekoop, Eberhart Zrenner, Randal J. Kaufman, Stephen H. Tsang, Bernd Wissinger, Jonathan H. Lin
Article
Ophthalmology
Stanley Lambertus, Ramon A. C. van Huet, Nathalie M. Bax, Lies H. Hoefsloot, Frans P. M. Cremers, Camiel J. F. Boon, B. Jeroen Klevering, Carel B. Hoyng
Article
Biochemistry & Molecular Biology
Kinga M. Bujakowska, Qi Zhang, Anna M. Siemiatkowska, Qin Liu, Emily Place, Marni J. Falk, Mark Consugar, Marie-Elise Lancelot, Aline Antonio, Christine Lonjou, Wassila Carpentier, Saddek Mohand-Said, Anneke I. den Hollander, Frans P. M. Cremers, Bart P. Leroy, Xiaowu Gai, Jose-Alain Sahel, L. Ingeborgh van den Born, Rob W. J. Collin, Christina Zeitz, Isabelle Audo, Eric A. Pierce
HUMAN MOLECULAR GENETICS
(2015)
Article
Genetics & Heredity
Nathalie M. Bax, Riccardo Sangermano, Susanne Roosing, Alberta A. H. J. Thiadens, Lies H. Hoefsloot, L. Ingeborgh van den Born, Milan Phan, B. Jeroen Klevering, Carla Westeneng-van Haaften, Terry A. Braun, Marijke N. Zonneveld-Vrieling, Ilse de Wijs, Merve Mutlu, Edwin M. Stone, Anneke I. den Hollander, Caroline C. W. Klaver, Carel B. Hoyng, Frans P. M. Cremers
Article
Multidisciplinary Sciences
Maleeha Maria, Muhammad Ajmal, Maleeha Azam, Nadia Khalida Waheed, Sorath Noorani Siddiqui, Bilal Mustafa, Humaira Ayub, Liaqat Ali, Shakeel Ahmad, Shazia Micheal, Alamdar Hussain, Syed Tahir Abbas Shah, Syeda Hafiza Benish Ali, Waqas Ahmed, Yar Muhammad Khan, Anneke I. den Hollander, Lonneke Haer-Wigman, Rob W. J. Collin, Muhammad Imran Khan, Raheel Qamar, Frans P. M. Cremers
Article
Genetics & Heredity
Sanne K. Verbakel, Zeinab Fadaie, B. Jeroen Klevering, Maria M. van Genderen, Ilse Feenstra, Frans P. M. Cremers, Card B. Hoyng, Susanne Roosing
MOLECULAR GENETICS & GENOMIC MEDICINE
(2019)
Article
Genetics & Heredity
Zeinab Fadaie, Mubeen Khan, Marta Del Pzo-oValero, Stephanie S. Cornelis, Carmen Ayuso, Frans P. M. Cremers, Susanne Roosing, Rando Allikmets, Miriam Bauwens, Mohammad Ghofrani, Michael B. Gorin, Mohammad Keramatipour, Francesca Simonelli, Naeimeh Tayebi, Andrea Vincent, Nicole Weisschuh
Review
Ophthalmology
Frans P. M. Cremers, Winston Lee, Rob W. J. Collin, Rando Allikmets
PROGRESS IN RETINAL AND EYE RESEARCH
(2020)
Article
Genetics & Heredity
Tabea V. Riepe, Mubeen Khan, Susanne Roosing, Frans P. M. Cremers, Peter A. C. 't Hoen
Summary: Hereditary disorders are often caused by genetic variants affecting RNA splicing, but predicting the pathogenicity of variants in noncanonical splice sites and deep intronic regions is challenging. A study comparing splice prediction tools on variants in two genes found that SpliceRover and SpliceAI performed the best.
Review
Biochemistry & Molecular Biology
Suzanne E. de Bruijn, Zeinab Fadaie, Frans P. M. Cremers, Hannie Kremer, Susanne Roosing
Summary: The review outlines the historical development of molecular diagnosis of monogenic diseases and the evolution of DNA sequencing technologies from Sanger to next-generation sequencing to third-generation sequencing. It also highlights the potential of novel approaches like optical mapping and multiomics in identifying genetic defects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Janine Reurink, Jaap Oostrik, Marco Aben, Mariana Guimaraes Ramos, Emma van Berkel, Monika Oldak, Erwin van Wijk, Hannie Kremer, Susanne Roosing, Frans P. M. Cremers
Summary: This study aimed to expand the understanding of splicing events and assess a selected set of non-canonical splice site variants in USH2A. The results showed that these variants had an effect on pre-mRNA splicing, highlighting their significance in the genetic etiology of associated disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Melita Kaltak, Rocio Blanco-Garavito, Laurie L. Molday, Claire-Marie Dhaenens, Eric E. Souied, Gerard Platenburg, Jim Swildens, Robert S. Molday, Frans P. M. Cremers
Summary: This study investigated the exon skipping phenomenon of exon 17 in the ABCA4 gene associated with Stargardt disease (STGD1) and designed corresponding oligonucleotides to induce exon 17 skipping. The results showed that the deletion of exon 17 in ABCA4 does not result in the absence of protein activity and does not cause a severe STGD1 phenotype when in trans with a null allele. Therefore, the impact of severe variants in exon 17 can potentially be ameliorated by exon skipping using antisense oligonucleotides (AONs), generating partial ABCA4 activity in STGD1 patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Correction
Genetics & Heredity
Susanne Kohl, Ditta Zobor, Wei-Chieh Chiang, Nicole Weisschuh, Jennifer Staller, Irene Gonzalez Menendez, Stanley Chang, Susanne C. Beck, Marina Garcia Garrido, Vithiyanjali Sothilingam, Mathias W. Seeliger, Franco Stanzial, Francesco Benedicenti, Francesca Inzana, Elise Heon, Ajoy Vincent, Jill Beis, Tim M. Strom, Guenther Rudolph, Susanne Roosing, Anneke I. den Hollander, Frans P. M. Cremers, Irma Lopez, Huanan Ren, Anthony T. Moore, Andrew R. Webster, Michel Michaelides, Robert K. Koenekoop, Eberhart Zrenner, Randal J. Kaufman, Stephen H. Tsang, Bernd Wissinger, Jonathan H. Lin