AI Article Synopsis
- Cynomolgus macaques are used in preclinical studies due to their close evolutionary relationship with humans, but the molecular details of their drug transporters have not been fully explored.
- Researchers identified and characterized seven ABC transporters in cynomolgus macaques, finding high sequence similarities (96-98%) to their human counterparts.
- The study revealed similar gene structures, genomic organization, and specific tissue expression patterns for these transporters, suggesting meaningful molecular parallels between cynomolgus macaques and humans.
Article Abstract
Cynomolgus macaques are used in preclinical studies in part because of their evolutionary closeness to humans. However, drug transporters, including ATP-binding cassette (ABC) transporters, which are essential for the absorption and excretion of drugs, have not been fully investigated at the molecular level in cynomolgus macaques. In this study, ABCB4, ABCC3, ABCC4, and ABCG2 cDNAs were newly identified and characterized, along with ABCB1, ABCB11, and ABCC2 cDNAs previously identified, in cynomolgus macaques. All seven cynomolgus ABC transporters had high sequence identities (96-98%) with their human orthologs in terms of amino acid sequences and were also most closely clustered with their human orthologs by phylogenetic analysis. Furthermore, the gene structures and genomic organization were similar in cynomolgus macaques and humans. The mRNAs of these cynomolgus ABC transporters, as analyzed using the quantitative polymerase chain reaction, showed distinct tissue expression patterns. Among the ten tissues, ABCB1, ABCC2, ABCC3, and ABCG2 mRNAs were most abundantly expressed in jejunum; ABCB4 and ABCB11 in liver; and ABCC4 in kidney, which are similar to the expression patterns of human ABC transporters. These results suggest molecular similarities of the ABC transporters in cynomolgus macaques and humans.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.dmpk.2021.100431 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
programmed myeloid cells expressing novel chimeric antigen receptors show potent anti-tumor activity in preclinical solid tumor models.
Front Immunol
December 2024
Myeloid Therapeutics, Inc., Cambridge, MA, United States.
Introduction: The approval of chimeric antigen receptor (CAR) T cell therapies for the treatment of B cell malignancies has fueled the development of numerous cell therapies. However, these cell therapies are complex and costly, and unlike in hematological malignancies, outcomes with most T cell therapies in solid tumors have been disappointing. Here, we present a novel approach to directly program myeloid cells by administering novel TROP2 CAR mRNA encapsulated in lipid nanoparticles (LNPs).
View Article and Find Full Text PDFFirst Report of Microplastics in Wild Long-Tailed Macaque () Feces at Kosumpee Forest Park, Maha Sarakham, Thailand.
Vet Sci
December 2024
Departments of Psychology, Global Health, and Anthropology, Center for Global Field Study, and Washington National Primate Research Center, University of Washington, Seattle, WA 98195, USA.
Microplastic pollution is a global concern arising from the extensive production and use of plastics. The prevalence of microplastics (MPs) in the environment is escalating due in large part to the excessive use of plastics in various human-related activities. Consequently, animals are being exposed to MPs through dietary intake, which poses significant health risks to the wild populations.
View Article and Find Full Text PDFIntravitreal Administration of Avacincaptad Pegol in a Nonhuman Primate Model of Dry Age-Related Macular Degeneration.
Pharmacol Res Perspect
February 2025
Hamamatsu Pharma Research, Inc., Hamamatsu, Shizuoka, Japan.
The lack of effective treatments for dry age-related macular degeneration (AMD) is in part due to a lack of a preclinical animal model that recapitulates features of the clinical state including macular retinal pigment epithelium (RPE) degeneration, also known as geographic atrophy (GA). A nonhuman primate model of GA was developed and its responsiveness to an approved treatment, avacincaptad pegol (ACP), a complement C5 inhibitor, was evaluated. Intravitreal (ivt) administration of sodium iodate (SI) into one eye of male Macaca fascicularis leads to retinal areas (mm) of hyper- or hypo-autofluorescence.
View Article and Find Full Text PDFComparative assessment of the transduction efficiency and safety associated with the delivery of AAV9-GFP vector via lumbar puncture to cynomolgus macaques with and without anti-AAV9 pre-existing antibodies.
Mol Ther Methods Clin Dev
December 2024
Preclinical Safety (PCS), Novartis Biomedical Research, Cambridge, MA, USA.
Administration of AAV-based gene therapies into the intra-cerebrospinal fluid (CSF) compartments via routes such as lumbar puncture (LP) has been implemented as an alternative to intravenous dosing to target the CNS regions. This route enables lower doses, decreases systemic toxicity, and circumvents intravascular pre-existing anti-AAV antibodies. In this study, AAV9-GFP vectors were administered via LP to juvenile cynomolgus macaques with and without pre-existing serum anti-AAV9 antibodies at a 5.
View Article and Find Full Text PDFHyperactivation of human acidic chitinase (Chia) for potential medical use.
J Biol Chem
December 2024
Department of Chemistry and Life Science, Kogakuin University, Hachioji, Tokyo, 192-0015, Japan. Electronic address:
Accumulation of environmental chitin in the lungs can lead to pulmonary fibrosis, characterized by inflammatory infiltration and fibrosis in acidic chitinase (Chia)-deficient mice. Transgenic expression of Chia in these mice ameliorated the symptoms, indicating the potential of enzyme supplementation as a promising therapeutic strategy for related lung diseases. This study focuses on utilizing hyperactivated human Chia, which exhibits low activity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!