Article
Microbiology
Archana Thomas, Ariel M. Slifka, Sara M. Hendrickson, Ian J. Amanna, Mark K. Slifka
Summary: Diphtheria is rare in the United States and many industrialized nations due to effective vaccines and high vaccination coverage. However, in several European countries, C. ulcerans has become the dominant source of diphtheria cases. This study identified active transmission of toxigenic C. ulcerans among rhesus macaques and provided evidence of potential human transmission. These findings highlight the importance of maintaining high vaccination coverage to reduce the risk of zoonotic infection.
MICROBIOLOGY SPECTRUM
(2022)
Article
Neurosciences
David Goertsen, Nicholas C. Flytzanis, Nick Goeden, Miguel R. Chuapoco, Alexander Cummins, Yijing Chen, Yingying Fan, Qiangge Zhang, Jitendra Sharma, Yangyang Duan, Liping Wang, Guoping Feng, Yu Chen, Nancy Y. Ip, James Pickel, Viviana Gradinaru
Summary: The study developed AAV capsids that achieved robust transgene expression in the brain with decreased liver targeting after non-invasive administration, enabling more targeted systemic gene delivery. This organ-specific targeting extends to marmosets, allowing for non-invasive gene delivery with distinct transgene expression patterns. The ability to cross the blood-brain barrier with neuronal specificity in rodents and non-human primates opens up new avenues for basic research and therapeutic possibilities beyond naturally occurring serotypes.
NATURE NEUROSCIENCE
(2022)
Article
Medicine, Research & Experimental
Petr O. Ilyinskii, Alicia M. Michaud, Gina L. Rizzo, Christopher J. Roy, Sheldon S. Leung, Stephanie L. Elkins, Teresa Capela, Aparajita Chowdhury, Lina Li, Randy J. Chandler, Irini Manoli, Eva Andres-Mateos, Lloyd P. M. Johnston, Luk H. Vandenberghe, Charles P. Venditti, Takashi Kei Kishimoto
Summary: The co-administration of ImmTOR and AAV demonstrates the potential to suppress immune responses, enhance transduction, and improve therapeutic outcomes in treating diseases caused by genetic mutations. This combination therapy could have promising clinical applications for patients with MMUT gene mutations and other genetic disorders.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Biotechnology & Applied Microbiology
Adam Beharry, Yi Gong, James C. Kim, Killian S. Hanlon, Josette Nammour, Kate Hieber, Florian Eichler, Ming Cheng, Anat Stemmer-Rachamimov, Konstantina M. Stankovic, Duane Bradley Welling, Carrie Ng, Casey A. Maguire
Summary: The AAV-F capsid shows slightly higher transgene expression in the spinal cord compared to AAV9, with lower numbers of genomes still able to mediate high expression levels. However, the efficiency of dorsal root ganglion transduction is lower for AAV-F than AAV9. Interestingly, AAV-F also demonstrates transduction of Schwann cells in the sciatic nerve, a phenomenon not observed with AAV9.
HUMAN GENE THERAPY
(2022)
Article
Multidisciplinary Sciences
Javier Blesa, Jose A. Pineda-Pardo, Ken-ichi Inoue, Carmen Gasca-Salas, Tiziano Balzano, Natalia Lopez-Gonzalez Del Rey, Alejandro Reinares-Sebastian, Noelia Esteban-Garcia, Rafael Rodriguez-Rojas, Raquel Marquez, Maria Ciorraga, Marta del Alamo, Lina Garcia-Canamaque, Santiago Ruiz de Aguiar, Itay Rachmilevitch, Ines Trigo-Damas, Masahiko Takada, Jose A. Obeso
Summary: Successful blood-brain barrier opening and targeted delivery of adeno-associated virus serotype 9 vectors into brain regions involved in Parkinson's disease were achieved using low-intensity focused ultrasound. Neuronal green fluorescent protein expression was observed specifically in regions with confirmed blood-brain barrier opening. This less-invasive methodology could potentially revolutionize gene therapy for neurodegenerative disorders.
Review
Immunology
Thomas Weber
Summary: AAV vector-based gene therapy is currently the only approved in vivo gene therapy in the US and Europe, but the presence of pre-existing anti-AAV antibodies presents a formidable challenge to its successful clinical use. Establishing protocols to determine relevant titers of these antibodies and methods to deplete them is now more urgent than ever to ensure the efficacy of AAV gene transfer therapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Jieyu Qi, Liyan Zhang, Fangzhi Tan, Yang Zhang, Yinyi Zhou, Ziyu Zhang, Hongyang Wang, Chaorong Yu, Lulu Jiang, Jiancheng Liu, Tian Chen, Lianqiu Wu, Shanzhong Zhang, Sijie Sun, Shan Sun, Ling Lu, Qiuju Wang, Renjie Chai
Summary: This study demonstrates the effectiveness and safety of OTOF gene therapy drugs in mice and nonhuman primates. The researchers developed a new strategy to deliver OTOF and successfully restored hearing in mice with profound deafness. The therapy also showed no impact on normal hearing and systemic toxicity in both mice and nonhuman primates.
Article
Microbiology
Nerea Zabaleta, Wenlong Dai, Urja Bhatt, Cecile Herate, Pauline Maisonnasse, Jessica A. Chichester, Julio Sanmiguel, Reynette Estelien, Kristofer T. Michalson, Cheikh Diop, Dawid Maciorowski, Nathalie Dereuddre-Bosquet, Mariangela Cavarelli, Anne-Sophie Gallouet, Thibaut Naninck, Nidhal Kahlaoui, Julien Lemaitre, Wenbin Qi, Elissa Hudspeth, Allison Cucalon, Cecilia D. Dyer, M. Betina Pampena, James J. Knox, Regina C. LaRocque, Richelle C. Charles, Dan Li, Maya Kim, Abigail Sheridan, Nadia Storm, Rebecca Johnson, Jared Feldman, Blake M. Hauser, Vanessa Contreras, Romain Marlin, Raphael Ho Tsong Fang, Catherine Chapon, Sylvie van der Werf, Eric Zinn, Aisling Ryan, Dione T. Kobayashi, Ruchi Chauhan, Marion McGlynn, Edward T. Ryan, Aaron G. Schmidt, Brian Price, Anna Honko, Anthony Griffiths, Sam Yaghmour, Robert Hodge, Michael R. Betts, Mason W. Freeman, James M. Wilson, Roger Le Grand, Luk H. Vandenberghe
Summary: The AAVCOVID-1 vaccine candidate demonstrates potent immunogenicity in animal experiments and provides complete protection against SARS-CoV-2 in macaques. It has sustained neutralizing antibody responses and functional memory T cell responses, with no cross-reactivity to common AAVs used in gene therapy.
CELL HOST & MICROBE
(2021)
Review
Biochemistry & Molecular Biology
Elena S. B. Campbell, Melanie M. Goens, Wenguang Cao, Brad Thompson, Leonardo Susta, Logan Banadyga, Sarah K. Wootton
Summary: Monoclonal antibodies (mAbs) are crucial in preventing and treating infectious diseases, especially when vaccines or therapies are lacking. Recent developments in mAb gene cloning have resulted in highly potent mAbs against various pathogens. Adeno-associated virus (AAV) vectors have been explored as a platform for delivering mAb genes, but further optimization is needed for improved therapeutic efficacy. This review summarizes the current landscape of AAV vectored immunoprophylaxis (VIP) in nonhuman primate (NHP) models and discusses major obstacles and implications for clinical translation.
Article
Medicine, Research & Experimental
Divya Ail, Duohao Ren, Elena Brazhnikova, Celine Nouvel-Jaillard, Stephane Bertin, Seyed Bagher Mirashrafi, Sylvain Fisson, Deniz Dalkara
Summary: This study investigates the potential inflammatory responses in AAV-mediated retinal gene therapy and the correlation between pre-existing serum antibodies and clinical outcomes. The results show a dose-dependent increase in antibodies after injection, and a correlation between serum antibody levels, inflammation, and transgene expression.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Virology
Darrick L. Yu, Natalie S. M. Chow, Byram W. Bridle, Sarah K. Wootton
Summary: Systemic delivery of liposome-encapsulated clodronate prior to AAV vector administration reduced transgene expression in the liver and heart, but allowed moderate transduction in the white pulp of the spleen. The immune system plays a significant role in influencing the distribution and relative numbers of transduced cells in AAV-mediated gene delivery, as demonstrated by the localization of transgene expression in different tissues.
Article
Medicine, Research & Experimental
Michael R. Emami, Alejandro Espinoza, Courtney S. Young, Feiyang Ma, Philip K. Farahat, Philip L. Felgner, Jeffrey S. Chamberlain, Xiangmin Xu, April D. Pyle, Matteo Pellegrini, S. Armando Villalta, Melissa J. Spencer
Summary: High systemic doses of AAVs have been associated with immune-related SAEs. Mice dual-dosed with AAV9 at 4-week intervals can better recapitulate aspects of human immunity to AAV. Activation of myeloid cells through Fcg receptors and/or complement receptors is one mechanism by which anti-AAV antigen complexes may prime antigen-presenting cells and amplify downstream immunity.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Biotechnology & Applied Microbiology
Dhwanil A. Dalwadi, Andrea Calabria, Amita Tiyaboonchai, Jeffrey Posey, Willscott E. Naugler, Eugenio Montini, Markus Grompe
Summary: Research found a high frequency of chromosomal integrations of recombinant adeno-associated viral vectors in liver cells, with most inserted sequences heavily rearranged and accompanied by deletions of host genomic sequences at integration sites. This indicates a certain risk associated with rAAV integration.
Article
Immunology
Kevin O. Saunders, Norbert Pardi, Robert Parks, Sampa Santra, Zekun Mu, Laura Sutherland, Richard Scearce, Maggie Barr, Amanda Eaton, Giovanna Hernandez, Derrick Goodman, Michael J. Hogan, Istvan Tombacz, David N. Gordon, R. Wes Rountree, Yunfei Wang, Mark G. Lewis, Theodore C. Pierson, Chris Barbosa, Ying Tam, Xiaoying Shen, Guido Ferrari, Georgia D. Tomaras, David C. Montefiori, Drew Weissman, Barton F. Haynes
Summary: mRNA-LNP vaccines show promising immunogenicity in inducing polyfunctional antibodies against HIV-1 and Zika virus, with even low doses being effective in macaques. Such vaccines may offer superior or comparable immunogenicity compared to adjuvanted recombinant protein vaccines in primates.
Article
Biology
Stephen Johnston, Sarah L. Parylak, Stacy Kim, Nolan Mac, Christina Lim, Iryna Gallina, Cooper Bloyd, Alexander Newberry, Christian D. Saavedra, Ondrej Novak, J. Tiago Goncalves, Fred H. Gage, Matthew Shtrahman
Summary: The study demonstrated that neural progenitor cells and immature dentate granule cells in the adult murine hippocampus are highly sensitive to rAAV-induced cell death, which is dose-dependent and nearly complete at experimentally relevant viral titers. rAAV-induced cell death is rapid and persistent, with no evidence of recovery of adult neurogenesis at 3 months post-injection.
Article
Hematology
Amelia R. Wilhelm, Nicole A. Parsons, Benjamin J. Samelson-Jones, Robert J. Davidson, Charles T. Esmon, Rodney M. Camire, Lindsey A. George
Summary: This study compared an APC-resistant FVIII variant with wild-type FVIII, and found that APC plays an important role in the in vivo regulation of FVIIIa, which could be exploited for developing novel treatments for hemophilia A.
Article
Pediatrics
Chelsea Kotch, David F. Friedman, Benjamin J. Wilkins, Benjamin J. Samelson-Jones
Summary: HDFN-associated cholestasis can result in extreme laboratory abnormalities, including extreme hyperferritinemia. Conservative management without iron chelation may be appropriate in some infants with these conditions.
Article
Hematology
Mary M. Robinson, Lindsey A. George, Marcus E. Carr, Benjamin J. Samelson-Jones, Valder R. Arruda, John E. Murphy, Denis Rybin, Jeremy Rupon, Katherine A. High, Stefan Tiefenbacher
Summary: Differences in FIX:C levels were observed with different assay methods in hemophilia B patients receiving FIX-Padua gene therapy, with local laboratory results strongly correlating with central laboratory results and consistently lower absolute values at the central lab. Fixation of FIX:C values was seen across different assays, with Actin FSL APTT reagent resulting in lower values at the central lab, and the chromogenic assay showing the lowest FIX:C values. Compared with expected values, rHFIX-Padua protein-spiked samples showed similar results while rHFIX-nonacog alfa results fell below 25% in the chromogenic assay.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Meeting Abstract
Hematology
Ben J. Samelson-Jones, Spencer K. Sullivan, John E. J. Rasko, Adam Giermasz, Lindsey A. George, Jonathan M. Ducore, Jerome M. Teitel, Catherine E. McGuinn, Amanda O'Brien, Ian Winburn, Lynne M. Smith, Amit Chhabra, Jeremy Rupon
Article
Hematology
Robert Chen, Kavitha Muralidharan, Benjamin J. Samelson-Jones
Summary: This study aims to assess the types of users and major themes in the haemophilia community on Twitter.
Article
Medicine, General & Internal
Lindsey A. George, Paul E. Monahan, M. Elaine Eyster, Spencer K. Sullivan, Margaret Ragni, Stacy E. Croteau, John E. J. Rasko, Michael Recht, Benjamin J. Samelson-Jones, Amy MacDougall, Kristen Jaworski, Robert Noble, Marla Curran, Klaudia Kuranda, Federico Mingozzi, Tiffany Chang, Kathleen Z. Reape, Xavier M. Anguela, Katherine A. High
Summary: A gene therapy trial using an AAV vector (SPK-8011) for factor VIII expression in 18 men with hemophilia A showed sustained expression in most participants, leading to reduced bleeding events and discontinuation of prophylaxis.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Letter
Oncology
Kaoru Takasaki, David Hehir, Leslie Raffini, Benjamin J. Samelson-Jones, Evelyn Shih, Aleksandra Sarah Dain
PEDIATRIC BLOOD & CANCER
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Erika J. Mejia, Matthew J. O'Connor, Benjamin J. Samelson-Jones, Constantine D. Mavroudis, Therese M. Giglia, Rachel Keashen, Joseph Rossano, Maryam Y. Naim, Katsuhide Maeda
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2022)
Editorial Material
Hematology
Benjamin J. Samelson-Jones
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Horacio Padua, Anne Marie Cahill, Rush Chewning, Elizabeth A. Himes, Kamlesh Kukreja, Riten Kumar, Francis Marshalleck, Eric Monroe, Sheena Patel, Benjamin J. Samelson-Jones, Raja Shaikh
Summary: This article provides guidance on the use of anticoagulant and antithrombotic agents in pediatric patients undergoing interventional radiology procedures. Through a comprehensive review of relevant studies, recommendations were developed and consensus agreement was reached. The article emphasizes the importance of considering the nuances of anticoagulation in pediatric practice.
JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
(2022)
Meeting Abstract
Hematology
Lucas Van Gorder, Bhavya S. Doshi, Elinor Willis, Matthew Lanza, Valder R. Arruda, Mary Beth Callan, Ben J. Samelson-Jones
Meeting Abstract
Hematology
Bhavya S. Doshi, Ben J. Samelson-Jones, Timothy C. Nichols, Elizabeth P. Merricks, Valder R. Arruda, Mary Beth Callan
Meeting Abstract
Hematology
Kyumin Lee, Julia Q. Chau, Anna R. Sternberg, Allyson M. Pishko, Lindsey George, Ben J. Samelson-Jones
Review
Hematology
Leonard A. Valentino, Margareth C. Ozelo, Roland W. Herzog, Nigel S. Key, Allyson M. Pishko, Margaret Ragni, Benjamin J. Samelson-Jones, David Lillicrap
Summary: The therapeutic landscape for people living with hemophilia A has changed, but there are still unmet medical needs in regards to FVIII inhibitors and ITI treatment. Emicizumab and gene therapy have emerged as potential options for improving treatment strategies and effectiveness.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
E. J. Mejia, M. J. O'Connor, C. D. Mavroudis, B. J. Samelson-Jones, T. M. Giglia, R. Keashen, J. W. Rossano, M. Y. Naim, K. Maeda
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2022)