Potential inhibition of HIV-1 encapsidation by oligoribonucleotide–dendrimer nanoparticle complexes

Raveen Parboosing,1,2 Louis Chonco,1,2 Francisco Javier de la Mata,3,4 Thavendran Govender,5 Glenn EM Maguire,5 Hendrik G Kruger5 1Department of Virology, University of KwaZulu-Natal, 2National Health Laboratory Service, Durban, South Africa; 3Organic and Inorganic Chemistry Department, University...

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Autores principales: Parboosing R, Chonco L, de la Mata FJ, Govender T, Maguire GEM, Kruger HG
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Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:7e51b875d143498289c5dc1084ecedbf2021-12-02T03:58:39ZPotential inhibition of HIV-1 encapsidation by oligoribonucleotide–dendrimer nanoparticle complexes1178-2013https://doaj.org/article/7e51b875d143498289c5dc1084ecedbf2017-01-01T00:00:00Zhttps://www.dovepress.com/potential-inhibition-of-hiv-1-encapsidation-by-oligoribonucleotide-den-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Raveen Parboosing,1,2 Louis Chonco,1,2 Francisco Javier de la Mata,3,4 Thavendran Govender,5 Glenn EM Maguire,5 Hendrik G Kruger5 1Department of Virology, University of KwaZulu-Natal, 2National Health Laboratory Service, Durban, South Africa; 3Organic and Inorganic Chemistry Department, University of Alcalá, Alcalá de Henares, 4Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; 5Catalysis and Peptide Research Unit, University of KwaZulu-Natal, Durban, South Africa Background: Encapsidation, the process during which the genomic RNA of HIV is packaged into viral particles, is an attractive target for antiviral therapy. This study explores a novel nanotechnology-based strategy to inhibit HIV encapsidation by an RNA decoy mechanism. The design of the 16-mer oligoribonucleotide (RNA) decoy is based on the sequence of stem loop 3 (SL3) of the HIV packaging signal (Ψ). Recognition of the packaging signal is essential to the encapsidation process. It is theorized that the decoy RNA, by mimicking the packaging signal, will disrupt HIV packaging if efficiently delivered into lymphocytes by complexation with a carbosilane dendrimer. The aim of the study is to measure the uptake, toxicity, and antiviral activity of the dendrimer–RNA nanocomplex. Materials and methods: A dendriplex was formed between cationic carbosilane dendrimers and the RNA decoy. Uptake of the fluorescein-labeled RNA into MT4 lymphocytes was determined by flow cytometry and confocal microscopy. The cytoprotective effect (50% effective concentration [EC50]) and the effect on HIV replication were determined in vitro by the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and viral load measurements, respectively. Results: Flow cytometry and confocal imaging demonstrated efficient transfection of lymphocytes. The dendriplex containing the Ψ decoy showed some activity (EC50 =3.20 µM, selectivity index =8.4). However, there was no significant suppression of HIV viral load. Conclusion: Oligoribonucleotide decoys containing SL3 of the packaging sequence are efficiently delivered into lymphocytes by carbosilane dendrimers where they exhibit a modest cytoprotective effect against HIV infection. Keywords: packaging signal, dendrimers, transfection, antiretroviral, HIV packagingParboosing RChonco Lde la Mata FJGovender TMaguire GEMKruger HGDove Medical PressarticlePackaging signaldendrimerstransfectionantiretroviralHIV packagingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 317-325 (2017)
institution DOAJ
collection DOAJ
language EN
topic Packaging signal
dendrimers
transfection
antiretroviral
HIV packaging
Medicine (General)
R5-920
spellingShingle Packaging signal
dendrimers
transfection
antiretroviral
HIV packaging
Medicine (General)
R5-920
Parboosing R
Chonco L
de la Mata FJ
Govender T
Maguire GEM
Kruger HG
Potential inhibition of HIV-1 encapsidation by oligoribonucleotide–dendrimer nanoparticle complexes
description Raveen Parboosing,1,2 Louis Chonco,1,2 Francisco Javier de la Mata,3,4 Thavendran Govender,5 Glenn EM Maguire,5 Hendrik G Kruger5 1Department of Virology, University of KwaZulu-Natal, 2National Health Laboratory Service, Durban, South Africa; 3Organic and Inorganic Chemistry Department, University of Alcalá, Alcalá de Henares, 4Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; 5Catalysis and Peptide Research Unit, University of KwaZulu-Natal, Durban, South Africa Background: Encapsidation, the process during which the genomic RNA of HIV is packaged into viral particles, is an attractive target for antiviral therapy. This study explores a novel nanotechnology-based strategy to inhibit HIV encapsidation by an RNA decoy mechanism. The design of the 16-mer oligoribonucleotide (RNA) decoy is based on the sequence of stem loop 3 (SL3) of the HIV packaging signal (Ψ). Recognition of the packaging signal is essential to the encapsidation process. It is theorized that the decoy RNA, by mimicking the packaging signal, will disrupt HIV packaging if efficiently delivered into lymphocytes by complexation with a carbosilane dendrimer. The aim of the study is to measure the uptake, toxicity, and antiviral activity of the dendrimer–RNA nanocomplex. Materials and methods: A dendriplex was formed between cationic carbosilane dendrimers and the RNA decoy. Uptake of the fluorescein-labeled RNA into MT4 lymphocytes was determined by flow cytometry and confocal microscopy. The cytoprotective effect (50% effective concentration [EC50]) and the effect on HIV replication were determined in vitro by the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and viral load measurements, respectively. Results: Flow cytometry and confocal imaging demonstrated efficient transfection of lymphocytes. The dendriplex containing the Ψ decoy showed some activity (EC50 =3.20 µM, selectivity index =8.4). However, there was no significant suppression of HIV viral load. Conclusion: Oligoribonucleotide decoys containing SL3 of the packaging sequence are efficiently delivered into lymphocytes by carbosilane dendrimers where they exhibit a modest cytoprotective effect against HIV infection. Keywords: packaging signal, dendrimers, transfection, antiretroviral, HIV packaging
format article
author Parboosing R
Chonco L
de la Mata FJ
Govender T
Maguire GEM
Kruger HG
author_facet Parboosing R
Chonco L
de la Mata FJ
Govender T
Maguire GEM
Kruger HG
author_sort Parboosing R
title Potential inhibition of HIV-1 encapsidation by oligoribonucleotide–dendrimer nanoparticle complexes
title_short Potential inhibition of HIV-1 encapsidation by oligoribonucleotide–dendrimer nanoparticle complexes
title_full Potential inhibition of HIV-1 encapsidation by oligoribonucleotide–dendrimer nanoparticle complexes
title_fullStr Potential inhibition of HIV-1 encapsidation by oligoribonucleotide–dendrimer nanoparticle complexes
title_full_unstemmed Potential inhibition of HIV-1 encapsidation by oligoribonucleotide–dendrimer nanoparticle complexes
title_sort potential inhibition of hiv-1 encapsidation by oligoribonucleotide–dendrimer nanoparticle complexes
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/7e51b875d143498289c5dc1084ecedbf
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