Over the past decades, remarkable progress on phosphoramidite chemistry-based large-scale oligonucleotide synthesis has been achieved, enabling numerous novel and exciting applications. Among them, genome synthesis and DNA data storage are striking. However, to make these two applications more practical, the synthesis length, speed, cost, and throughput require vast improvements, which is a challenge to be met by the phosphoramidite chemistry. Harnessing the power of enzymes, the recently emerged enzymatic methods provide a competitive route to overcome this challenge. In this review, we first summarize the status of large-scale oligonucleotide synthesis technologies including the basic methodology and large-scale synthesis approaches, with special focus on the emerging enzymatic methods. Afterward, we discuss the opportunities and challenges of large-scale oligonucleotide synthesis on genome synthesis and DNA data storage respectively.
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http://dx.doi.org/10.3389/fbioe.2021.689797 | DOI Listing |
Nat Commun
January 2025
School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.
Chip scale DNA synthesis offers a high-throughput and cost-effective method for large-scale DNA-based information storage. Nevertheless, unbiased information retrieval from low-copy-number sequences remains a barricade that largely arises from the indispensable DNA amplification. Here, we devise a simulation-guided quantitative primer-template hybridization strategy to realize massively parallel homogeneous amplification of chip-scale DNA for DNA information storage (MPHAC-DIS).
View Article and Find Full Text PDFAgeing Res Rev
January 2025
i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain; Physical Activity and Health Research Group (PaHerg), Research Institute of the Hospital 12 de Octubre ('imas12'), Madrid 28041, Spain. Electronic address:
Accumulating evidence suggests that gut microbiota (GM) plays a crucial role in Alzheimer's disease (AD) pathogenesis and progression. This narrative review explores the complex interplay between GM, the immune system, and the central nervous system in AD. We discuss mechanisms through which GM dysbiosis can compromise intestinal barrier integrity, enabling pro-inflammatory molecules and metabolites to enter systemic circulation and the brain, potentially contributing to AD hallmarks.
View Article and Find Full Text PDFInt J Med Sci
January 2025
Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, People's Republic of China.
Elevated lipoprotein(a) [Lp(a)] levels are increasingly recognized as a significant risk factor for cardiovascular diseases and may also contribute to atrial fibrillation (AF). This review investigated the indirect mechanisms through which Lp(a) may influence AF, including proatherogenic, prothrombotic, and proinflammatory pathways. Traditional lipid-lowering therapies, such as lifestyle modifications and statins, have limited effects on Lp(a) levels.
View Article and Find Full Text PDFMolecules
December 2024
NRC Institute of Immunology FMBA of Russia, 115552 Moscow, Russia.
N-Acetylgalactosamine (GalNAc) is an efficient and multifunctional delivery tool in the development and synthesis of chemically modified oligonucleotide therapeutics (conjugates). Such therapeutics demonstrate improved potency in vivo due to the selective and efficient delivery to hepatocytes in the liver via receptor-mediated endocytosis, which is what drives the high interest in this molecule. The ways to synthesize such structures are relatively new and have not been optimized in terms of the yields and stages both in lab and large-scale synthesis.
View Article and Find Full Text PDFNatl Sci Rev
January 2025
Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
The long-term preservation of large volumes of infrequently accessed cold data poses challenges to the storage community. Deoxyribonucleic acid (DNA) is considered a promising solution due to its inherent physical stability and significant storage density. The information density and decoding sequence coverage are two important metrics that influence the efficiency of DNA data storage.
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