Id |
Subject |
Object |
Predicate |
Lexical cue |
T59 |
0-112 |
Sentence |
denotes |
Beyond targeting the surface proteins of 2019-nCoV, one could also target the RNA genome itself for degradation. |
T60 |
113-376 |
Sentence |
denotes |
This RNA genome sequence of 2019-nCoV was recently published (GenBank: MN908947.3), and one strategy that could be considered then, is the use of small interfering RNA (siRNA) or antisense oligonucleotides (ASO) to combat the virus by targeting its RNA genome 23. |
T61 |
377-424 |
Sentence |
denotes |
The challenge with this strategy is multi-fold. |
T62 |
425-493 |
Sentence |
denotes |
First, the conserved RNA sequence domains of CoV-2019 are not known. |
T63 |
494-631 |
Sentence |
denotes |
Identifying conserved sequences is essential in order to optimize siRNA targeting and avoid viral escape of the oligonucleotide strategy. |
T64 |
632-770 |
Sentence |
denotes |
One could look at genome homology of 2019-nCoV to the SARS virus for comparison of conserved sequences, but this would still be guesswork. |
T65 |
771-852 |
Sentence |
denotes |
A second challenge is how the oligonucleotides would be delivered into the lungs. |
T66 |
853-977 |
Sentence |
denotes |
Advances have been made into delivery vehicles such as lipid nanoparticles that can mediate some delivery into the lungs 24. |
T67 |
978-1143 |
Sentence |
denotes |
It is unknown, however, if enough siRNA’s or ASO’s would be effectively delivered within the lungs to stop the infection or make a difference in its clinical course. |
T68 |
1144-1360 |
Sentence |
denotes |
For example, if 25% of alveolar epithelial cells in the lung had siRNA or ASO in them, that efficiency might be a great success for traditional gene therapy, but would hardly make any difference in a viral infection. |
T69 |
1361-1516 |
Sentence |
denotes |
Such an explanation is also likely why siRNA candidates against Ebola failed in trials 25, despite significant success in preclinical animal models 26, 27. |
T70 |
1517-1681 |
Sentence |
denotes |
Lastly, even if one assumed that siRNA was effective clinically, there is a limited ability to scale up manufacturing of siRNA drugs to a large infected population. |
T71 |
1682-1835 |
Sentence |
denotes |
Current siRNA and ASO therapies are manufactured for rare diseases, and there are no available resources existing to manufacture the medications quickly. |