Generation of HIV-Resistant Macrophages from IPSCs by Using Transcriptional Gene Silencing and Promoter-Targeted RNA

Molecular Therapy. Nucleic Acids
Kei HigakiShin Kaneko

Abstract

Highly active antiretroviral therapy (HAART) has markedly prolonged the prognosis of HIV-1 patients. However, lifelong dependency on HAART is a continuing challenge, and an effective therapeutic is much desired. Recently, introduction of short hairpin RNA (shRNA) targeting the HIV-1 promoter was found to suppress HIV-1 replication via transcriptional gene silencing (TGS). The technology is expected to be applied with hemato-lymphopoietic cell transplantation of HIV patients to suppress HIV transcription in transplanted hemato-lymphopoietic cells. Combination of the TGS technology with new cell transplantation strategy with induced pluripotent stem cell (iPSC)-derived hemato-lymphopoietic cells might contribute to new gene therapy in the HIV field. In this study, we evaluated iPSC-derived macrophage functions and feasibility of TGS technology in macrophages. Human iPSCs were transduced with shRNAs targeting the HIV-1 promoter region (shPromA) by using a lentiviral vector. The shPromA-transfected iPSCs were successfully differentiated into functional macrophages, and they exhibited strong protection against HIV-1 replication with alteration in the histone structure of the HIV-1 promoter region to induce heterochromatin formation....Continue Reading

Citations

Apr 4, 2021·Life Sciences·Mohsen SheykhhasanMassoud Saidijam
Apr 20, 2021·Molecular Therapy. Methods & Clinical Development·Yoshihiro IwamotoShin Kaneko

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
fluorescence microscopy
FACS
PCR
immunoprecipitation
transfection
acetylation
flow cytometry

Software Mentioned

CASAVA
FlowJo
RPKMforGenes
PromA
TopHat
BCL2FASTQ Conversion

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