title: Potential inhibition of HIV-1 encapsidation by oligoribonucleotide-dendrimer nanoparticle complexes.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Virology, University of KwaZulu-Natal; National Health Laboratory Service, Durban, South Africa.
authors.forename: Raveen
authors.initials: R
authors.lastname: Parboosing
authors.affiliation: Department of Virology, University of KwaZulu-Natal; National Health Laboratory Service, Durban, South Africa.
authors.forename: Louis
authors.initials: L
authors.lastname: Chonco
authors.affiliation: Organic and Inorganic Chemistry Department, University of Alcalá, Alcalá de Henares; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: de la Mata
authors.affiliation: Catalysis and Peptide Research Unit, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Thavendran
authors.initials: T
authors.lastname: Govender
authors.affiliation: Catalysis and Peptide Research Unit, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Glenn Em
authors.initials: GE
authors.lastname: Maguire
authors.affiliation: Catalysis and Peptide Research Unit, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Kruger
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D005434:Flow Cytometry; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D053758:Nanoparticles / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D009843:Oligoribonucleotides / Q000494:pharmacology*; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D012821:Silanes / Q000737:chemistry; D014162:Transfection; D019562:Viral Load / Q000187:drug effects; D019065:Virus Assembly / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D050091:Dendrimers; D009843:Oligoribonucleotides; D012367:RNA, Viral; D012821:Silanes; C504072:carbosilane
keywords: HIV packaging; antiretroviral; dendrimers; packaging signal; transfection