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Reti, D.

Publications and source records attributed to Reti, D..

2 recordsLinked to original sources

But Mouse, you are not alone: On some severe acute respiratory syndrome coronavirus 2 variants infecting mice

In silico predictions combined with in vitro, in vivo and in situ observations collectively suggest that mouse adaptation of the SARS-CoV-2 virus requires an aromatic substitution in position 501 or position 498 (but not both) of the spike proteins receptor binding domain. This effect could be enhanced by mutations in positions 417, 484, and 493 (especially K417N, E484K, Q493K and Q493R), and to a lesser extent by mutations in positions 486 and 499 (such as F486L and P499T). Such enhancements due to more favourable binding interactions with residues on the complementary angiotensin-converting enzyme 2 (ACE2) interface, are however, unlikely to sustain mouse infectivity on their own based on theoretical and experimental evidence to date. Our current understanding thus points to the Alpha, Beta, Gamma, and Omicron variants of concern infecting mice, while Delta and Delta Plus lack a similar biomolecular basis to do so. This paper identifies eleven countries (Brazil, Chile, Djibouti, Haiti, Malawi, Mozambique, Reunion, Suriname, Trinidad and Tobago, Uruguay and Venezuela) where targeted local field surveillance of mice is encouraged because they may have come in contact with humans who had the virus with adaptive mutation(s). It also provides a systematic methodology to analyze the potential for other animal reservoirs and their likely locations.

bioinformatics↗

Optimized nickase- and nuclease-based prime editing in human and mouse cells

Precise genomic modification using prime editing (PE) holds enormous potential for research and clinical applications. Currently, the delivery of PE components to mammalian cell lines requires multiple plasmid vectors. To overcome this limitation, we generated all-in-one prime editing (PEA1) constructs that carry all the components required for PE, along with a selection marker. We tested these constructs (with selection) in HEK293T, K562, HeLa and mouse embryonic stem (ES) cells. We discovered that PE efficiency in HEK293T cells was much higher than previously observed, reaching up to 95% (mean 67%). The efficiency in K562 and HeLa cells, however, remained low. To improve PE efficiency in K562 and HeLa, we generated a nuclease prime editor and tested this system in these cell lines as well as mouse ES cells. PE-nuclease greatly increased prime editing initiation, however, installation of the intended edits was often accompanied by extra insertions derived from the repair template. Finally, we show that zygotic injection of the nuclease prime editor can generate correct modifications in mouse fetuses with up to 100% efficiency. In summary, PE-nuclease and the PEA1 plasmids provide new tools to generate intended edits with high efficiency.

molecular biology↗