Article
Biology
Motoi Kato, Shohei Ishikawa, Qi Shen, Zening Du, Takuya Katashima, Mitsuru Naito, Takao Numahata, Mutsumi Okazaki, Takamasa Sakai, Masakazu Kurita
Summary: Researchers have developed a PEG-based carrier, called PEG slime, which enables localized delivery of rAAV to mouse skin ulcers with minimal off target delivery. This provides a new method for highly localized gene transduction.
COMMUNICATIONS BIOLOGY
(2023)
Review
Medicine, Research & Experimental
Darnel Prakoso, Mitchel Tate, Miles J. De Blasio, Rebecca H. Ritchie
Summary: Diabetes increases the prevalence of heart failure by 6-8-fold, independent of other comorbidities, such as hypertension and coronary artery disease, leading to a condition known as diabetic cardiomyopathy. Current pharmacological treatments can delay disease progression, but gene therapy using adeno-associated viral vectors (AAV) is being explored as a potential lifelong cure for diabetic cardiomyopathy.
Article
Medicine, Research & Experimental
Peng Zou
Summary: This study compared the performance of two allometric scaling approaches and a body-weight-based dose conversion approach for dose prediction in gene therapy. The body-weight-based approach underestimated the dose in some vectors, while the allometric scaling approach overestimated the dose. The allometric scaling between log GEF and W-0.25 was appropriate in certain conditions.
MOLECULAR PHARMACEUTICS
(2023)
Article
Biotechnology & Applied Microbiology
Yasuhiro Naiki, Mami Miyado, Miyuki Shindo, Reiko Horikawa, Yuichi Hasegawa, Noriyuki Katsumata, Shuji Takada, Hidenori Akutsu, Masafumi Onodera, Maki Fukami
Summary: Congenital adrenal hyperplasia (CAH) is a genetic disorder caused by enzyme defects. This study investigated the potential of gene induction in the adrenal glands to ameliorate CAH, and found that it may be effective for microsomal P450 defects but may require adrenal gene induction for mitochondrial P450 defects.
HUMAN GENE THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Melad Farraha, Renuka Rao, Sindhu Igoor, Thi Y. L. Le, Michael A. Barry, Christopher Davey, Cindy Kok, James J. H. Chong, Eddy Kizana
Summary: This study aimed to develop a biological alternative to electronic pacemakers by using gene therapy to convert cardiomyocytes into sinoatrial node-like cells. The results showed that the transduction of hTBX18 gene resulted in morphological, molecular, physiological, and functional changes in the cardiomyocytes, recapitulating the pacemaker phenotype. The use of a clinically relevant vector opens new prospects for the development of biological pacemakers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Amedee Mollard, Cecile Peccate, Anne Forand, Julie Chassagne, Laura Julien, Pierre Meunier, Zoheir Guesmia, Thibaut Marais, Marc Bitoun, France Pietri-Rouxel, Sofia Benkhelifa-Ziyyat, Stephanie Lorain
Summary: The study focused on the impact of the necrosis-regeneration process on the efficiency of AAV therapy, finding that regenerated muscles showed reduced transgene expression, which may limit the application of AAV-based therapies.
SCIENTIFIC REPORTS
(2022)
Article
Cardiac & Cardiovascular Systems
Michael G. Katz, Yoav Hadas, Rasheed A. Bailey, Shahood Fazal, Adam Vincek, Sophia J. Madjarova, Nataly Shtraizent, Luk H. Vandenberghe, Efrat Eliyahu
Summary: The study demonstrates that Anc80L65 is an efficient vector for cardiac gene therapy, providing fast and robust gene transduction compared with adeno-associated virus, serotype 9 vector. Anc80L65 does not adversely affect cardiac function or cause inflammatory response or toxicity.
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
(2022)
Article
Integrative & Complementary Medicine
Gai Ran, Xi-lin Feng, Yi-lin Xie, Qing-yun Zheng, Peng-peng Guo, Ming Yang, Ying-lu Feng, Chen Ling, Li-qing Zhu, Chen Zhong
Summary: By overexpressing miR122 in HEK293 cells and incorporating the 122T sequence, it is possible to attenuate the expression of cytotoxic transgenes during rAAV vector production, leading to an increased production yield of rAAV vectors.
JOURNAL OF INTEGRATIVE MEDICINE-JIM
(2021)
Article
Biochemistry & Molecular Biology
Francesco Aulicino, Martin Pelosse, Christine Toelzer, Julien Capin, Erwin Ilegems, Parisa Meysami, Ruth Rollarson, Per-Olof Berggren, Mark Simon Dillingham, Christiane Schaffitzel, Moin A. Saleem, Gavin Welsh, Imre Berger
Summary: This article addresses the challenge of delivering multiple components into living cells for precise gene-editing. The researchers utilize baculovirus, which has a high cargo capacity, to successfully replace multiple exons and restore protein expression in cells derived from patients with nephrotic syndrome. The study also demonstrates the efficient search and replace of DNA without detectable indels.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Neurosciences
Zhong-Rui Chen, Jing-Ying Guo, Lu He, Shan Liu, Jun-Yi Xu, Zi-Jing Yang, Wei Su, Ke Liu, Shu-Sheng Gong, Guo-Peng Wang
Summary: Dual-AAV-ie vectors allow efficient co-transduction in the vestibular sensory epithelium and facilitate the delivery of large or multiple genes for vestibular gene therapy.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Zachary C. Elmore, L. Patrick Havlik, Daniel K. Oh, Leif Anderson, George Daaboul, Garth W. Devlin, Heather A. Vincent, Aravind Asokan
Summary: The membrane-associated accessory protein (MAAP) is identified as a novel viral egress factor that promotes the secretion of AAV serotypes. MAAP contains a cationic amphipathic domain critical for AAV secretion. Restoring MAAP expression can rescue the secretion defect in various AAV serotypes with mutated start sites.
NATURE COMMUNICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
Zhiquan Xiang, Klaudia Kuranda, William Quinn, Areski Chekaoui, Robert Ambrose, Mohadeseh Hasanpourghai, Mikhail Novikov, Dakota Newman, Christina Cole, Xiangyang Zhou, Federico Mingozzi, Hildegund C. J. Ertl
Summary: Adeno-associated virus (AAV) vector-mediated gene transfer is effective in treating monogenetic disorders, but immune responses to AAV or the therapeutic protein encoded by it often occur in recipients. In this study, the researchers explored the use of immunosuppressants rapamycin and ibrutinib, alone or in combination, to inhibit antibody responses specific to AAV vector or transgene product.
HUMAN GENE THERAPY
(2022)
Article
Biotechnology & Applied Microbiology
Sang-oh Han, Dorothy Gheorghiu, Alex Chang, Sweet Hope Mapatano, Songtao Li, Elizabeth Brooks, Dwight Koeberl
Summary: This study found that adding testosterone during gene therapy can significantly improve neuromuscular function, muscle strength, and biochemical indicators in female mice with Pompe disease, while oxandrolone has a certain improvement effect on biochemical indicators. These data confirm the benefits of brief androgen hormone treatment during gene therapy in mice with Pompe disease.
HUMAN GENE THERAPY
(2022)
Review
Clinical Neurology
Robert Duba-Kiss, Yosuke Niibori, David R. Hampson
Summary: This Mini Review discusses the use of various gene regulatory elements for targeting GABAergic neurons, with a focus on adeno-associated viral vectors, the most widely used class of viral vectors for treating brain diseases.
FRONTIERS IN NEUROLOGY
(2021)
Article
Chemistry, Analytical
Zhijie Wu, Hongxia Wang, Andrew Tustian, Haibo Qiu, Ning Li
Summary: Adeno-associated viruses (AAVs) have emerged as an attractive vector for gene therapy applications. To support process development and product characterization, a new online two-dimensional liquid chromatography-mass spectrometry method was developed for AAV characterization.
ANALYTICAL CHEMISTRY
(2022)
Letter
Clinical Neurology
Mathieu Cerino, Emmanuelle Salort-Campana, Svetlana Gorokhova, Amandine Sevy, Nathalie Bonello-Palot, Nicolas Levy, Shahram Attarian, Marc Bartoli, Martin Krahn
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2021)
Article
Genetics & Heredity
Alexandra Salvi, Cristina Skrypnyk, Nathalie Da Silva, Jon Andoni Urtizberea, Moiz Bakhiet, Catherine Robert, Nicolas Levy, Andre Megarbane, Valerie Delague, Marc Bartoli
Summary: Bi-allelic mutations in the STIM1 gene result in CRAC channelopathy syndrome, characterized by symptoms such as muscle weakness and hyperlaxity. A novel homozygous frameshift mutation in STIM1, identified in this study, leads to complete loss of the STIM1 protein. The findings broaden the spectrum of phenotypes associated with STIM1 mutations.
Article
Genetics & Heredity
Theo Charnay, Veronique Blanck, Mathieu Cerino, Marc Bartoli, Florence Riccardi, Nathalie Bonello-Palot, Christophe Pecheux, Karine Nguyen, Nicolas Levy, Svetlana Gorokhova, Martin Krahn
Summary: Recent advances in sequencing technologies and the establishment of international standards for variant interpretation have led to a significant shift in diagnostic approaches in clinical genetics. However, the reclassification of variants that were originally considered pathogenic is still lacking in scientific literature and variant databases, hindering the interpretation of diagnostic sequencing results.
GENETICS IN MEDICINE
(2021)
Editorial Material
Physiology
Alexandra Salvi, Andre Maues De Paula, Nicolas Levy, Shahram Attarian, Marc Bartoli
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Medical Laboratory Technology
Khaoula Rochdi, Mathieu Cerino, Nathalie Da Silva, Valerie Delague, Aymane Bouzidi, Halima Nahili, Ghizlane Zouiri, Yamna Kriouile, Svetlana Gorokhova, Marc Bartoli, Rachid Saile, Abdelhamid Barakat, Martin Krahn
Summary: This study identified novel homozygous mutations associated with neuromuscular disorders in two Moroccan families. The use of next-generation sequencing combined with Sanger sequencing allowed for a better understanding of the genetic diversity and disease mechanisms underlying these disorders. The study reported the first identified SIL1 mutation in the Moroccan population, which was found to be the main cause of Marinesco-Sjogren syndrome. Additionally, a mutation in the fatty acid 2-hydroxylase gene (FA2H) was associated with Spastic paraplegia 35. The findings contribute to the phenotypic spectrum and diagnostic orientation of patients with neuromuscular disorders.
CLINICA CHIMICA ACTA
(2022)
Article
Biochemistry & Molecular Biology
Nathalie Bourg, Ai Vu Hong, William Lostal, Abbass Jaber, Nicolas Guerchet, Guillaume Tanniou, Fanny Bordier, Emilie Bertil-Froidevaux, Christophe Georger, Nathalie Daniele, Isabelle Richard, David Israeli
Summary: Duchenne muscular dystrophy (DMD) is a common and incurable muscle genetic disease, and therapeutic approaches have focused on restoring dystrophin expression. However, the efficacy of this treatment is still unsatisfactory, potentially due to unresolved technical issues and the progressive nature of DMD. Recent research has identified abnormalities in the mevalonate pathway and cholesterol metabolism in DMD patients, which can be improved by simvastatin treatment. This study investigated the additive beneficial effect of dystrophin restoration and simvastatin treatment, but no additional benefit was observed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Transplantation
Stanislas Bataille, Laetitia Dou, Marc Bartoli, Marion Sallee, Julien Aniort, Borhane Ferkak, Rania Chermiti, Nathalie McKay, Nathalie Da Silva, Stephane Burtey, Stephane Poitevin
Summary: In chronic kidney disease (CKD), the plasma concentrations of myostatin and activin A are increased, possibly due to reduced renal clearance. Furthermore, we observed increased production of activin A in the kidney and heart, which may be related to muscle wasting. Therefore, myostatin and activin A should be added to the list of uremic toxins.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2022)
Article
Neurosciences
Remi Bos, Khalil Rihan, Patrice Quintana, Lara El-Bazzal, Nathalie Bernard-Marissal, Nathalie Da Silva, Rosette Jabbour, Andre Megarbane, Marc Bartoli, Frederic Brocard, Valerie Delague
Summary: This study found that mutations in VRK1 affect the action potential waveform and axonal initial segment organization in patients. These findings are important for understanding the mechanisms of the related motor neuron disease.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Maude Vecten, Emmanuelle Pion, Marc Bartoli, Raul Juntas Morales, Damien Sternberg, John Rendu, Tanya Stojkovic, Cecile Acquaviva Bourdain, Corinne Metay, Isabelle Richard, Mathieu Cerino, Mathieu Milh, Emmanuelle Campana-Salort, Svetlana Gorokhova, Nicolas Levy, Xenia Latypova, Gisele Bonne, Valerie Biancalana, Francois Petit, Annamaria Molon, Aurelien Perrin, Pascal Laforet, Shahram Attarian, Martin Krahn, Mireille Cossee
Summary: The implementation of high-throughput diagnostic sequencing has led to challenges in interpretation of mutational data, calling for prioritization of gene analysis in diagnostic and management settings. Objective assessment of clinical actionability of genes in myopathies using ClinGen scoring method provided important insights for diagnostic approaches and genetic disease management.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Mario Abaji, Svetlana Gorokhova, Nathalie Da Silva, Tiffany Busa, Maude Grelet, Chantal Missirian, Sabine Sigaudy, Nicole Philip, France Leturcq, Nicolas Levy, Martin Krahn, Marc Bartoli
Summary: Exon skipping is a promising therapeutic approach, where it is crucial to ensure the exon-skipped form of the gene can partially perform the required function and improve phenotype. Discovery of a deletion of in-frame exon 49 in the DMD gene opens up possibilities to extend exon skipping approaches for patients carrying truncating mutations in exon 49.
Article
Genetics & Heredity
Mathieu Cerino, Patricio Gonzalez-Hormazabal, Mario Abaji, Sebastien Courrier, Francesca Puppo, Yves Mathieu, Alejandra Trangulao, Nicholas Earle, Claudia Castiglioni, Jorge Diaz, Mario Campero, Ricardo Hughes, Carmen Vargas, Rocio Cortes, Karin Kleinsteuber, Ignacio Acosta, J. Andoni Urtizberea, Nicolas Levy, Marc Bartoli, Martin Krahn, Lilian Jara, Pablo Caviedes, Svetlana Gorokhova, Jorge A. Bevilacqua
Summary: This study reported the genetic findings of Chilean patients with limb-girdle muscle weakness. They identified definite genetic diagnoses in 59.8% of the patients and highly probable genetic diagnoses in 9.8% of the patients. The most frequent causative genes were DYSF and CAPN3. The relative frequency of different forms of myopathy in Chile is similar to that in other regions.
Article
Clinical Neurology
Lara El-Bazzal, Adeline Ghata, Clothilde Esteve, Jihane Gadacha, Patrice Quintana, Christel Castro, Nathalie Roeckel-Trevisiol, Frederique Lembo, Nicolas Lenfant, Andre Megarbane, Jean-Paul Borg, Nicolas Levy, Marc Bartoli, Yannick Poitelon, Pierre L. Roubertoux, Valerie Delague, Nathalie Bernard-Marissal
Summary: Charcot-Marie-Tooth (CMT) disease is a common inherited neurological disorder caused by mutations in over 100 genes. A study found that mutations in the FGD4 gene, which encodes FRABIN, can lead to aberrant myelination in the peripheral nervous system. The loss of FRABIN affects the NRG1/ERBB2/3 signaling pathway and impairs endocytic trafficking, contributing to myelination defects.
Article
Transplantation
Stanislas Bataille, Nathalie McKay, Laetitia Koppe, Alice Beau, Berengere Benoit, Marc Bartoli, Nathalie Da Silva, Stephane Poitevin, Julien Aniort, Rania Chermiti, Stephane Burtey, Laetitia Dou
Summary: Indoxyl sulfate (IS), an indolic uremic toxin, inhibits the expression of Myf6/MRF4 and MYH2 during muscle cell differentiation, leading to a defect in myotube structure. This provides new insights into the role of IS in muscle atrophy observed in CKD.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Biochemistry & Molecular Biology
Oceane Ballouhey, Marie Chapoton, Benedicte Alary, Sebastien Courrier, Nathalie Da Silva, Martin Krahn, Nicolas Levy, Noah Weisleder, Marc Bartoli
Summary: This study describes a new mouse model, Dysf (p.Y1159X/p.Y1159X), which carries several defects observed in dysferlinopathy patients and other published mouse models. This mutant mouse model is expected to be useful for testing various therapeutic approaches such as termination codon readthrough, pharmacological approaches, and exon skipping. Therefore, the data presented in this study strongly support the use of this animal model for the development of preclinical strategies for the treatment of dysferlinopathies.
Meeting Abstract
Biochemistry & Molecular Biology
Maude Vecten, Emmanuelle Pion, Raul Juntas Morales, Damien Sternberg, John Rendu, Tania Stojkovic, Cecile Acquaviva-Bourdain, Corrine Metay, Isabelle Richard, Laurent Villard, Mathieu Cerino, Mathieu Milh, Sevtlana Gorokhova, Nicolas Levy, Xenia Martin, Gisele Bonne, Valerie Biancalana, Francois Petit, Aurelien Perrin, Pascal Laforet, Marc Bartoli, Mireille Cossee, Martin Krahn
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)