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2014 ; 1
(4
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
HIV Excision Utilizing CRISPR/Cas9 Technology: Attacking the Proviral
Quasispecies in Reservoirs to Achieve a Cure
#MMPMID25893217
Dampier W
; Nonnemacher MR
; Sullivan NT
; Jacobson JM
; Wigdahl B
MOJ Immunol
2014[Oct]; 1
(4
): ä PMID25893217
show ga
Recently several gene-editing technologies developed are being explored for their
potential utility in providing new and unique treatments for HIV. One of these
technologies is the clustered regularly interspaced short palindromic repeats
(CRISPR)/CRISPR-associated (Cas)9 system. This system is being explored for its
utility against host genes important to HIV infection, namely the HIV coreceptor
CCR5, and for excision of the integrated genome from infected cells by targeting
selected genes or genomic regions, especially the HIV-1 promoter or long terminal
repeat (LTR). One of the major hurdles with the development of this technology
for use in patients is defining the LTR sequence spectrum within the viral
quasispecies present in the integrated virus and how that effects the number of
guide RNAs (gRNAs) required to completely excise all proviral genomes. In this
study, the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort
was utilized to demonstrate that [1] the predominant sequence of the integrated
proviral LTR within the PBMC compartment shows a decrease in the amount of
variation per year regardless of the type of therapy; [2] predominant HIV-1 LTR
sequence undergoes continued genetic change with respect to the predominant
genotype in these cells for at least 6 years while on effective suppressive ART;
[3] using next generation sequencing (NGS), to demonstrate that 4 of the 8
patient samples examined could have a complete gRNA regimen designed to target
all known quasispecies; and [4] length of HAART therapy may reduce the number of
gRNA required to eradicate provirus as shown by NGS and gRNA design for
longitudinal samples of patient A0017 in the CARES cohort. Overall, these studies
demonstrate the feasibility of addressing at least one of the major technological
challenges of CRISPR/Cas9-mediated HIV-1 proviral genome eradication involving
the effective targeting of all viral quasispecies in a given patient sample.