Review
Biochemistry & Molecular Biology
Betul Celik, Kader Cicek, Andres Felipe Leal, Shunji Tomatsu
Summary: Osteosarcoma is the most common malignant bone tumor affecting adolescents and young adults, requiring the development of novel targeted therapies for relapse cases. RNA interference technologies show promise in cancer treatment by silencing overexpressed genes to induce apoptosis in tumor cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Yoshiaki Kobayashi, Shen Tian, Kumiko Ui-Tei
Summary: In RNA interference (RNAi), small interfering RNA (siRNA) can suppress the expression of both target mRNA and unintended mRNAs. Previous studies have shown that the off-target effect is induced through stable base-pairing between the siRNA seed region and off-target mRNAs. However, a recent study revealed that the siRNA seed region consists of two functionally different domains: nucleotides 2-5, essential for off-target effects, and nucleotides 6-8, involved in both RNAi and off-target effects.
Article
Environmental Sciences
Bo Yan, Hua Zhang, Luping Xu, Yu Chen, Hongmin Lu
Summary: The developed 4D TBD approach aims to track weak extended targets in cluttered environments. It addresses the challenges of high dimensional measurements, as well as heterogeneous background clutter and clutter regions. Experimental results demonstrate the effectiveness of the method in detecting close targets with a high detection rate.
Article
Plant Sciences
Bo Shen, Monica A. Schmidt, Kristin Haug Collet, Zhan-Bin Liu, Monique Coy, Shane Abbitt, Lynda Molloy, Mary Frank, John D. Everard, Russ Booth, Partha P. Samadar, Yonghua He, Anthony Kinney, Eliot M. Herman
Summary: Silencing soybean AIP2 genes can enhance seed protein content without affecting seed oil content by regulating the activity of the ABI3 transcription factor protein. This gene-editing prototype shows potential to improve global food security and protein availability in soybean and other protein-source crops.
JOURNAL OF EXPERIMENTAL BOTANY
Review
Physiology
Matthew W. Kay, Vivek Jain, Gurusher Panjrath, David Mendelowitz
Summary: This review summarizes the evidence linking autonomic imbalance to cardiorespiratory diseases, with a focus on reduced parasympathetic activity. It also discusses potential mechanisms and targets for restoring parasympathetic activity and improving cardiorespiratory health, from myocytes to the brain.
Article
Cell Biology
Robert G. Bristow, Joanne Engel, Izzy Jayasinghe, Martin Kampmann, Owen James Sansom, David M. Bryant
Summary: This article introduces LGBT+ History Month in February, and describes a conversation organized by David Bryant, a member of the Journal of Cell Science Editorial Advisory Board, with a group of scientists to discuss their experiences as LGBT+ individuals in academia.
JOURNAL OF CELL SCIENCE
(2022)
Article
Neurosciences
Thieu X. Phan, Hoai T. Ton, Hajnalka Gulyas, Robert Porszasz, Attila Toth, Rebekah Russo, Matthew W. Kay, Niaz Sahibzada, Gerard P. Ahern
Summary: Arterioles maintain blood flow by adjusting their diameter in response to changes in local blood pressure, and TRPV1 plays a critical role in this process.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Surgery
Peter A. Than, Christopher R. Davis, Robert C. Rennert, Shane D. Morrison, Michael W. Findlay, Mark A. Kay, Geoffrey C. Gurtner
Summary: This study achieved systemic gene delivery by transfecting rat superficial inferior epigastric artery flaps, opening up new possibilities for treating protein deficiency disorders.
PLASTIC AND RECONSTRUCTIVE SURGERY
(2022)
Article
Biochemistry & Molecular Biology
Marcus Y. Chin, Kean-Hooi Ang, Julia Davies, Carolina Alquezar, Virginia G. Garda, Brendan Rooney, Kun Leng, Martin Kampmann, Michelle R. Arkin, Aimee W. Kao
Summary: The study aimed to identify small molecules that acidify lysosomal pH and molecular targets/pathways that regulate lysosomal pH. Using a new lysosomal pH biosensor, a high-throughput screening assay identified two compounds, OSI-027 and PP242, as top acidifying hits, which may be used to investigate potential therapeutic pathways for neurodegenerative diseases such as autophagy activation and lysosomal acidification.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Developmental Biology
Annika Balraj, Cheryl Clarkson-Paredes, Ahdeah Pajoohesh-Ganji, Matthew W. Kay, David Mendelowitz, Robert H. Miller
Summary: This study examines the relationship between axon conduction and myelination in the maturing optic nerve. The results show that axon diameter, ion channel subtype, and myelin thickness are key regulators of nerve function. These findings suggest an extended period of maturation in the normal optic nerve that facilitates the development of visual signaling patterns.
DEVELOPMENTAL NEUROBIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Shinnosuke Tsuji, Calvin J. Stephens, Giulia Bortolussi, Feijie Zhang, Gabriele Baj, Hagoon Jang, Gustavo de Alencastro, Andres F. Muro, Katja Pekrun, Mark A. Kay
Summary: The use of ribonucleotide reductase inhibitors can substantially enhance the efficiency of adeno-associated virus-mediated homologous recombination-based gene therapy. These findings suggest that clinically approved inhibitors, such as fludarabine, can be used to potentiate gene editing therapies.
NATURE BIOTECHNOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Denise E. Sabatino, Frederic D. Bushman, Randy J. Chandler, Ronald G. Crystal, Beverly L. Davidson, Ricardo Dolmetsch, Kevin C. Eggan, Guangping Gao, Irene Gil-Farina, Mark A. Kay, Douglas M. McCarty, Eugenio Montini, Adora Ndu, Jing Yuan
Summary: This paper reviews the evidence of host genome integration of recombinant AAV (rAAV) in animal models and the potential risks of insertional mutagenesis in patients, highlighting the need for further research, regulatory guidance, and patient care in the field of gene therapy.
Review
Genetics & Heredity
Kun Leng, Martin Kampmann
Summary: Our understanding of neurological diseases has been greatly improved by new technologies. Glial cells have been identified as important in diseases, and single-cell profiling technologies describe disease states of neurons and glia at a molecular level. However, there are still gaps in understanding the mechanisms and contributions of disease-associated cell states, which can be filled by CRISPR-based functional genomics.
Article
Medicine, Research & Experimental
Francesco Puzzo, Chuanling Zhang, Bethany Powell Gray, Feijie Zhang, Bruce A. Sullenger, Mark A. Kay
Summary: This study developed a new chemically modified AAV vector, N & epsilon;-AAVs, which allows post-production engineering through click chemistry. The functionalized N & epsilon;-AAVs showed increased transduction efficiency and demonstrated selective uptake in vivo, making them versatile gene therapy vectors for specific cell targeting.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Medicine, Research & Experimental
Ren Song, Katja Pekrun, Themasap A. Khan, Feijie Zhang, Sergiu P. Pasca, Mark A. Kay
Summary: The low penetration of recombinant adeno-associated virus (rAAV) vectors across the human blood-brain barrier (BBB) is a limitation for gene transfer into the central nervous system (CNS). Researchers have screened a capsid-shuffled library to identify improved capsids with enhanced penetration and transduction of cells in the CNS. They also identified specific amino acid regions associated with capsids selected for neurons and astrocytes, and discovered genes that affect the transcytosis of AAV across the BBB.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Letter
Biochemical Research Methods
Andrew D. Holmes, Patricia P. Chan, Qi Chen, Pavel Ivanov, Laurence Drouard, Norbert Polacek, Mark A. Kay, Todd M. Lowe
Article
Multidisciplinary Sciences
Adriana Gonzalez-Sandoval, Katja Pekrun, Shinnosuke Tsuji, Feijie Zhang, King L. Hung, Howard Y. Chang, Mark A. Kay
Summary: The effectiveness of rAAV vectors varies between species, and a single amino acid change in the vector can alter its epigenomic state and transgene expression levels between species.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Jie Yang, Kelsey R. Baron, Daniel E. Pride, Anette Schneemann, Xiaoyan Guo, Wenqian Chen, Albert S. Song, Giovanni Aviles, Martin Kampmann, R. Luke Wiseman, Gabriel C. Lander
Summary: In this study, researchers discovered that the cleavage product of DELE1 induced by mitochondrial stress forms a signaling platform that triggers the integrated stress response. They determined the cryo-electron microscopy structure of the C-terminal cleavage product of human DELE1, which assembles into a high-order oligomer. The assembly-impaired DELE1 mutants were found to have compromised activation of HRI-dependent integrated stress response.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)