Erythrocytes as carriers of antisense PNA addressed against HIV-1 gag-pol transframe domain.
PNA(PR2) is a peptide nucleic acid (PNA) complementary to a sequence of the viral protease-encoding gene, effective in blocking HIV release, when used at high doses. Erythrocytes (RBC) were used to target PNA(PR2) to the macrophage compartment. The antiviral activity was assessed in human HIV-infected macrophages both as inhibition of p24 production and reduction of HIV DNA content. PNA(PR2), either added to the medium at a concentration of 100 microM or loaded into RBC at about 40 microM, inhibited p24 production approximately 80% compared with infected samples and reduced HIV DNA content by 83% and 90%, respectively. The results show that (1) a stronger anti-HIV effect is achievable with higher doses of PNA(PR2), both when given free and encapsulated into RBC; (2) the antiviral effect obtained by free PNA(PR2) at a concentration of 100 microM is achievable by encapsulating it into RBC at a concentration of 40 microM, suggesting that RBC can be used as a delivery system to increase the antisense effect of PNA(PR2).
Fraternale
Alessandra
A
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, PU, Italy. alessandra.fraternale@uniurb.it
Paoletti
Maria Filomena
MF
Casabianca
Anna
A
Orlandi
Chiara
C
Millo
Enrico
E
Balestra
Emanuela
E
Damonte
Gianluca
G
Perno
Carlo Federico
CF
Magnani
Mauro
M
D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology; D004279:DNA, Viral / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000737:chemistry*; D015685:Fusion Proteins, gag-pol / Q000187:drug effects / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000821:virology; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology; D020135:Peptide Nucleic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D055815:Young Adult; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000187:drug effects
D019380:Anti-HIV Agents; D004279:DNA, Viral; D004337:Drug Carriers; D015685:Fusion Proteins, gag-pol; D016655:HIV Core Protein p24; D016376:Oligonucleotides, Antisense; D020135:Peptide Nucleic Acids; D054301:gag Gene Products, Human Immunodeficiency Virus