id7b00244_si_002.xlsx (280.26 kB)
Genetically Validated Drug Targets in Leishmania: Current Knowledge and Future Prospects
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posted on 2018-01-31, 00:00 authored by Nathaniel G. Jones, Carolina M. C. Catta-Preta, Ana Paula C. A. Lima, Jeremy C. MottramThere has been a very limited number
of high-throughput screening campaigns carried out with Leishmania drug targets. In part, this is due to the small number of suitable
target genes that have been shown by genetic or chemical methods to
be essential for the parasite. In this perspective, we discuss the
state of genetic target validation in the field of Leishmania research and review the 200 Leishmania genes and
36 Trypanosoma cruzi genes for which gene deletion
attempts have been made since the first published case in 1990. We
define a quality score for the different genetic deletion techniques
that can be used to identify potential drug targets. We also discuss
how the advances in genome-scale gene disruption techniques have been
used to assist target-based and phenotypic-based drug development
in other parasitic protozoa and why Leishmania has
lacked a similar approach so far. The prospects for this scale of
work are considered in the context of the application of CRISPR/Cas9
gene editing as a useful tool in Leishmania.
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Future ProspectsGenetically Validated Drugdrug targetsCurrent Knowledgetarget validation200 Leishmania genesLeishmania drug targetstarget genesLeishmania researchphenotypic-based drug developmentgenome-scale gene disruption techniques36 Trypanosoma cruzi genesgene deletion attemptshigh-throughput screening campaignsCRISPRquality scoredeletion techniqueschemical methods