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Functional analysis of Plasmodium falciparum genome using morpholino‐based tools
Author(s) -
Garg Aprajita,
Kumar Vidya,
Wesolowski Donna,
Altman Sidney,
Mamoun Choukri
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.723.12
Subject(s) - morpholino , biology , rna splicing , plasmodium falciparum , rna interference , functional genomics , gene knockdown , computational biology , gene , microbiology and biotechnology , genome , genetics , rna , genomics , malaria , immunology
Malaria remains a major public health issue worldwide. Lack of an effective vaccine and rapid emergence of drug resistance are two major cause of this persistent problem. Understanding of the biology of the parasite is limited by the lack of functional tools to examine its gene function. Morpholino (MO)‐based tools are good alternatives to RNAi as the designed oligos are inherently stable and can down‐regulate gene expression by inducing cleavage of the mRNA or by inhibiting its splicing or translation. We have shown earlier that peptide‐morpholino oligomer (PMO) conjugate can target specific nuclear RNA ( PfGyrA) for degradation (1). We have further validated the use of PMO in an Apicoplast residing protein DXR, which indicates that PMOs can be targeted to different subcellular compartments. Morpholinos can also be designed to inhibit post‐transcriptional processing. We demonstrate inhibition of splicing of the transcripts of Phosphoethanolamine methyl transferase (PMT) and Chloroquine resistance transporter (CRT), leading to an increase in the defective spliced product and reduction in the functional transcript. The decrease in functional transcript led to defect in parasite growth. Along with functional analysis; we have examined interaction between MOs and some antimalarial drugs to assess the use of these conjugates in target validation and drug resistance reversal.