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Wachowius, F.

Publications and source records attributed to Wachowius, F..

2 recordsLinked to original sources

Highly potent antisense oligonucleotides (ASOs) targeting the SARS-CoV-2 RNA genome

Currently the world is dealing with the third outbreak of the human-infecting coronavirus with potential lethal outcome, cause by a member of the Nidovirus family, the SARS-CoV-2. The severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused the last worldwide pandemic. Successful development of vaccines highly contributed to reduce the severeness of the COVID-19 disease. To establish a control over the current and newly emerging coronaviruses of epidemic concern requires development of substances able to cure severely infected individuals and to prevent virus transmission. Here we present a therapeutic strategy targeting the SARS-CoV-2 RNA using antisense oligonucleotides (ASOs) and identify locked nucleic acid gapmers (LNA gapmers) potent to reduce by up to 96% the intracellular viral load in vitro. Our results strongly suggest promise of our preselected ASOs for further development as therapeutic or prophylactic anti-viral agents. One sentence summaryASOs (LNA gapmers) targeting the SARS-CoV-2 RNA genome have been effective in viral RNA (load) reduction in vitro.

molecular biology↗

Emergence of function from single RNA sequences by Darwinian evolution

The spontaneous emergence of function from pools of random sequence RNA is widely considered an important transition in the origin of life. However, the plausibility of this hypothetical process and the number of productive evolutionary trajectories in sequence space are unknown. Here we demonstrate that function can arise starting from a single RNA sequence by an iterative process of mutation and selection. Specifically, we describe the discovery of both specific ATP or GTP aptamers - with micromolar affinity for their nucleotide ligand - starting each from a single, homopolymeric poly-A sequence flanked by conserved primer binding sites. Our results indicate that the ab initio presence of large, diverse random sequence pools is not a prerequisite for the emergence of functional RNAs and that the process of Darwinian evolution has the capacity to generate function even from single, largely unstructured RNA sequences with minimal molecular and informational complexity.

synthetic biology↗