Article
Biochemistry & Molecular Biology
L. Belova, A. Demchenko, K. Kochergin-Nikitsky, E. Kondrateva, Ya. Slesarenko, D. Salikhova, A. Lavrov, A. Efremova, T. Bukharova, D. Goldshtein, S. Smirnikhina
Summary: Recombinant adeno-associated viruses (rAAVs) have potential for gene therapy, but their efficiency for transducing human induced pluripotent stem cells (hiPSCs) is unclear. In this study, we found that rAAV serotypes 5, 6, and 9 were not suitable for delivering transgenes into hiPSCs, as their transduction efficiency was very low compared to tracheal epithelial cells. These findings emphasize the need for further research to develop more efficient gene delivery methods for hiPSCs.
MOLECULAR BIOTECHNOLOGY
(2023)
Article
Medicine, Research & Experimental
Alexander Michels, Annika M. Frank, Dorothee M. Guenther, Mehryad Mataei, Kathleen Borner, Dirk Grimm, Jessica Hartmann, Christian J. Buchholz
Summary: This study successfully improved gene delivery efficiency to CD8+ mouse lymphocytes using mCD8-LV, based on DARPin binding to murine CD8. The results suggest a potential application of DARPins in AAV vectors for targeted gene therapy.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Review
Biochemistry & Molecular Biology
Lyubava Belova, Alexander Lavrov, Svetlana Smirnikhina
Summary: Cellular 3D structures, such as organoids, are important for biomedical research. However, there are challenges in delivering transgenes to these structures. This review explores ways to improve the efficiency of transgene delivery.
Article
Biotechnology & Applied Microbiology
Michelle Mendiola Pla, Yuting Chiang, Antonio Roki, Chunbo Wang, Franklin H. Lee, Matthew F. Smith, Ryan T. Gross, Jun-Neng Roan, Muath Bishawi, Amy Evans, Lynden E. Gault, Sam Ho, Carolyn Glass, Jacob N. Schroder, Paul Lezberg, Carmelo A. Milano, Dawn E. Bowles
Summary: This study demonstrates the feasibility and efficiency of delivering genes to porcine cardiac allografts utilizing adeno-associated viral vectors during ex vivo perfusion. Durable and dose-dependent transgene expression was achieved in the allografts, supporting the idea of gene therapy interventions to enhance transplantation outcomes.
HUMAN GENE THERAPY
(2023)
Article
Biochemical Research Methods
Aurelien Jacob, Laurie Brun, Paloma Jimenez Gil, Lucie Menard, Mohammed Bouzelha, Frederic Broucque, Aline Roblin, Luk H. Vandenberghe, Oumeya Adjali, Cecile Robin, Achille Francois, Veronique Blouin, Magalie Penaud-Budloo, Eduard Ayuso
Summary: Manufacturing viral vectors for gene delivery is challenging, with a scalable baculovirus-insect cell platform being used for producing rAAV vectors. A faster and safer method based on homologous recombination (HR) has been investigated to avoid technical constraints and safety concerns associated with the Tn7 transposition method. The HR system offers increased stability and avoids undesirable bacterial genes, ensuring the generation of safer rAAV biotherapeutic products.
BIOTECHNOLOGY JOURNAL
(2021)
Article
Engineering, Chemical
Abhiram Arunkumar, Nripen Singh
Summary: This study quantitatively investigated the ultrafiltration behavior of AAVs using different membrane molecular weight cut-off and operating conditions, showing that these factors can impact the flux and transmission of AAV. The study found that a 100 kDa ultrafiltration membrane can act as a completely retentive membrane or as significantly permeable to AAV serotypes depending on the operating conditions.
JOURNAL OF MEMBRANE SCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Amelie Bauer, Matteo Puglisi, Dennis Nagl, Joel A. Schick, Thomas Werner, Andreas Klingl, Jihad El Andari, Veit Hornung, Horst Kessler, Magdalena Goetz, Dirk Grimm, Ruth Brack-Werner
Summary: Astrocytes play crucial roles in the central nervous system and are involved in various CNS diseases. This study focuses on astrocyte-centered diseases and the need for effective and well-characterized gene transfer vectors. The findings highlight the use of a synthetic peptide-displaying AAV9 variant, rAAV9P1, which was shown to efficiently target and transduce human astrocytes. The study also identifies the specific receptors and intracellular pathways utilized by rAAV9P1 for astrocyte targeting. These results enhance our understanding of synthetic AAV vectors for astrocytes and their potential applications in research and medicine.
Review
Biotechnology & Applied Microbiology
Sha Sha, Andrew J. Maloney, Georgios Katsikis, Tam N. T. Nguyen, Caleb Neufeld, Jacqueline Wolfrum, Paul W. Barone, Stacy L. Springs, Scott R. Manalis, Anthony J. Sinskey, Richard D. Braatz
Summary: The article focuses on analyzing the bottlenecks in rAAV production during cell culture, comparing differences between wild-type and recombinant systems, and proposing future directions for improvement.
BIOTECHNOLOGY ADVANCES
(2021)
Review
Biochemistry & Molecular Biology
Karina Spunde, Ksenija Korotkaja, Anna Zajakina
Summary: Viral vectors are being studied as tools for cancer immunotherapy, but their clinical success is currently limited. Understanding the tumor immune state and developing vectors to modify the immunosuppressive tumor microenvironment are key elements for successful virus-based cancer immunotherapy. This review discusses DNA and RNA virus vectors delivering immunomodulatory genes and their potential to switch the tumor microenvironment to an immune-responsive state. The advantages and limitations of virus vectors for targeted therapeutic programming of tumor immune cell populations and tumor stroma are highlighted.
Article
Medicine, Research & Experimental
Sunghee Chai, Mason Norgard, Bin Li, David Enicks, Daniel L. Marks, Markus Grompe
Summary: Two small promoters have been discovered that can enable larger transgene expression than standard promoters, expanding the potential of clinical gene therapy.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Genetics & Heredity
Yang Wu, Zengpeng Han, Mingzhu Duan, Liangyu Jiang, Tiantian Tian, Dingyu Jin, Qitian Wang, Fuqiang Xu
Summary: The optimized single BEV-derived OneBac system allows for the efficient and scalable production of all serotypes of rAAV1-13, making it popular for laboratory scaling-up production.
CURRENT GENE THERAPY
(2021)
Article
Medicine, General & Internal
Dezhuang Ye, Jinyun Yuan, Yaoheng Yang, Yimei Yue, Zhongtao Hu, Siaka Fadera, Hong Chen
Summary: This study investigates the potential of focused ultrasound-mediated intranasal delivery (FUSIN) in delivering adeno-associated viral (AAV) vectors to the brain. The results show that FUSIN achieves safe and efficient delivery to spatially targeted brain locations and is comparable to established delivery methods.
Article
Nanoscience & Nanotechnology
Alicja Bienkowska-Tokarczyk, Maciej Malecki
Summary: Recombinant adeno-associated virus vectors (rAAV) are valuable as gene therapy vectors due to their nanometer size and biological characteristics. A mosaic vector, rAAV/DJ/CAG, showed efficient gene delivery to melanoma cells metastasized to the lungs, with transduction being temperature dependent. High temperatures and UV light had the most detrimental impact on transduction efficiency.
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
(2021)
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
Agriculture, Dairy & Animal Science
Seema Rani Pegu, Rajib Deb, Pranab Jyoti Das, Gyanendra Singh Sengar, Ajay Kumar Yadav, Swaraj Rajkhowa, Souvik Paul, Vivek Kumar Gupta
Summary: A diagnostic method for simultaneously detecting and distinguishing ASF, PCV2, and PPV in clinical specimens is crucial for differential diagnosis and control. The developed multiplex PCR assay demonstrated high accuracy in detecting these viruses in postmortem tissues from India's North Eastern region, revealing their co-circulation. The results also indicated the co-infection of ASF with PCV and PPV.
ANIMAL BIOTECHNOLOGY
(2023)
Article
Medicine, General & Internal
Michele Lanza, Luigi De Rosa, Sandro Sbordone, Rosa Boccia, Ugo Antonello Gironi Carnevale, Francesca Simonelli
Summary: This study evaluated the changes in corneal biomechanical properties after myopic refractive surgery, showing significant decreases in corneal hysteresis and corneal resistance factor after 1 month. Corvis ST parameters showed different evolution, indicating that corneal shape remodeling can continue up to 6 months post-surgery.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Urology & Nephrology
Miriam Zacchia, Francesca Del Vecchio Blanco, Annalaura Torella, Raffaele Raucci, Giancarlo Blasio, Maria Elena Onore, Emanuela Marchese, Francesco Trepiccione, Caterina Vitagliano, Valentina Di Iorio, Perna Alessandra, Francesca Simonelli, Vincenzo Nigro, Giovambattista Capasso, Davide Viggiano
Summary: This study revealed a high prevalence of renal dysfunction in patients with Bardet-Biedl syndrome, with urine concentrating defect potentially serving as a predictor of disease progression. However, the pathophysiology of hyposthenuria may not be directly linked to specific tubule dysfunctions.
CLINICAL KIDNEY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Raffaella Brunetti-Pierri, Marianthi Karali, Paolo Melillo, Valentina Di Iorio, Antonella De Benedictis, Gennarfrancesco Iaccarino, Francesco Testa, Sandro Banfi, Francesca Simonelli
Summary: Achromatopsia is a rare genetic disorder that affects cone photoreceptors, leading to progressive decline in visual acuity, macular sensitivity, and ERG responses. Structural integrity of the retina is also slowly affected over time. These findings can contribute to the development of guidelines for patient selection and intervention timing in gene replacement therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Claudio Iovino, Valentina Di Iorio, Francesco Testa, Viviana Bombace, Paolo Melillo, Kiran Kumar Vupparaboina, Jay Chhablani, Francesca Simonelli
Summary: This study analyzed the relationship between cystoid spaces and choroidal vascular features in patients with choroideremia. The results suggest that the choroid may not be involved in the development of cystoid spaces in patients with choroideremia.
Article
Genetics & Heredity
Tiziana Fioretti, Valentina Di Iorio, Barbara Lombardo, Francesca De Falco, Armando Cevenini, Fabio Cattaneo, Francesco Testa, Lucio Pastore, Francesca Simonelli, Gabriella Esposito
Summary: Choroideremia (CHM) is a genetic chorioretinal dystrophy caused by deficiencies in the CHM gene, with approximately 20% of patients having deletions in the gene. Analysis revealed repeat element hotspots associated with CHM gene rearrangements in some patients, and varying mutation types may affect disease mechanisms by altering the expression levels of CHM and CHML genes. Further research on the regulatory mechanisms of CHM and CHML gene expression could potentially aid in the development of effective therapies for this untreatable inherited retinal degeneration.
Article
Ophthalmology
Francesco Testa, Paolo Melillo, Michele Della Corte, Valentina Di Iorio, Raffaella Brunetti-Pierri, Amelia Citro, Maurizio Ferrara, Marianthi Karali, Rosa Annibale, Sandro Banfi, Settimio Rossi, Francesca Simonelli
Summary: Two Italian pediatric patients with RPE65-IRD treated with VN showed significant improvements in visual outcomes, including BCVA, FST test, SKVF, microperimetry, and chromatic pupillometry. Even in cases of surgical complications, recovery without sequelae was observed.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2021)
Article
Ophthalmology
Luigi Di Perna, Paolo Melillo, Carlo Gesualdo, Filomena Palmieri, Francesco Testa, Mario Bifani, Settimio Rossi, Francesca Simonelli
Summary: This study investigated the relationship between choriocapillaris perfusion and retinal sensitivity in eyes with intermediate age-related macular degeneration (iAMD). The results showed a significant association between lower values of perfused choriocapillaris and macular dysfunction, quantified by microperimetry, in iAMD eyes. OCT-A could be a useful tool for detecting choriocapillaris alterations and monitoring disease progression.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2021)
Article
Medicine, General & Internal
Raffaella Brunetti-Pierri, Marianthi Karali, Francesco Testa, Gerarda Cappuccio, Maria Elena Onore, Francesca Romano, Giuseppe De Rosa, Enrico Tedeschi, Nicola Brunetti-Pierri, Sandro Banfi, Francesca Simonelli
Summary: Pathogenic variants in the MKS1 gene can lead to a range of clinical manifestations from Meckel and Joubert syndrome to Bardet-Biedl syndrome. This case study highlights the use of clinical exome sequencing in identifying mild forms of a disease spectrum, such as mild JBTS with RP in an individual with biallelic truncating variants in MKS1.
Article
Multidisciplinary Sciences
Patrizia Tornabene, Rita Ferla, Manel Llado-Santaeularia, Miriam Centrulo, Margherita Dell'Anno, Federica Esposito, Elena Marrocco, Emanuela Pone, Renato Minopoli, Carolina Iodice, Edoardo Nusco, Settimio Rossi, Hristiana Lyubenova, Anna Manfredi, Lucio Di Filippo, Antonella Iuliano, Annalaura Torella, Giulio Piluso, Francesco Musacchia, Enrico Maria Surace, Davide Cacchiarelli, Vincenzo Nigro, Alberto Auricchio
Summary: The study introduces a novel gene therapy approach, AAV-HITI, to overcome challenges in gene therapy. The results show that AAV-HITI enables efficient gene integration in both retina and liver, leading to therapeutic benefits for genetic diseases.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Sabrina Carrella, Martina Di Guida, Simona Brillante, Davide Piccolo, Ludovica Ciampi, Irene Guadagnino, Jorge Garcia Piqueras, Mariateresa Pizzo, Elena Marrocco, Marta Molinari, Georgios Petrogiannakis, Sara Barbato, Yulia Ezhova, Alberto Auricchio, Brunella Franco, Elvira De Leonibus, Enrico Maria Surace, Alessia Indrieri, Sandro Banfi
Summary: The downregulation of miR-181a/b has beneficial effects on retinal diseases by promoting mitochondrial turnover and improving retinal morphology and function. This suggests that miR-181a/b downregulation could serve as an innovative mutation-independent therapeutic strategy for inherited retinal diseases.
EMBO MOLECULAR MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Anna Lorenzin, Luca Sgarabotto, Maria Laura Bacci, Alberto Elmi, Domenico Ventrella, Camilla Aniballi, Monica Zanella, Alessandra Brendolan, Luca Di Lullo, Claudio Ronco
Summary: This study presents a new miniaturized device called AD1 for extracorporeal ultrafiltration, designed for patients with fluid overload. The device operates at low pressure and flow regimes and has a user-friendly interface. The in vivo tests showed that it is safe, reliable, and accurate, opening up possibilities for clinical trials in various settings.
CARDIORENAL MEDICINE
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Eugenio Nahuel Pugni, Mariangela Lupo, Carolina Iodice, Carlo Gesualdo, Settimio Rossi, Francesca Simonelli, Maria Laura Bacci, Cesare Galli, Alberto Auricchio, Ivana Trapani
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Ophthalmology
Giuseppe De Rosa, Settimio Rossi, Carmine Santamaria, Rosa Boccia, Luigi De Rosa, Francesco Maria D'Alterio, Francesca Simonelli
Summary: Simultaneous topography-guided PRK with MMC 0.02% application and standard CXL is a safe, promising, and effective procedure in the treatment of mild and moderate keratoconus, leading to significant improvement in visual acuity and corneal curvature over a 2-year follow-up.
THERAPEUTIC ADVANCES IN OPHTHALMOLOGY
(2022)
Article
Ophthalmology
Francesco Testa, Vittoria Murro, Sabrina Signorini, Leonardo Colombo, Giancarlo Iarossi, Francesco Parmeggiani, Benedetto Falsini, Anna Paola Salvetti, Raffaella Brunetti-Pierri, Giorgia Aprile, Chiara Bertone, Agnese Suppiej, Francesco Romano, Marianthi Karali, Simone Donati, Paolo Melillo, Andrea Sodi, Luciano Quaranta, Luca Rossetti, Luca Buzzonetti, Marzio Chizzolini, Stanislao Rizzo, Giovanni Staurenghi, Sandro Banfi, Claudio Azzolini, Francesca Simonelli
Summary: This study investigated the development of inherited retinal degenerations (IRD) due to mutations in the RPE65 gene in an Italian population. By collecting data on visual acuity, visual field, and imaging, the study found a correlation between genotype and phenotype, which can contribute to better management of RPE65-associated IRD patients.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
