PNAPR2 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 PNAPR2 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. PNAPR2, either added to the medium at a concentration of 100 μM or loaded into RBC at about 40 μM, inhibited p24 production ~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 PNAPR2, both when given free and encapsulated into RBC; (2) the antiviral effect obtained by free PNAPR2 at a concentration of 100 μM is achievable by encapsulating it into RBC at a concentration of 40 μM, suggesting that RBC can be used as a delivery system to increase the antisense effect of PNAPR2.

Erythrocytes as carriers of antisense PNA addressed against HIV-1 gag-pol transframe domain

FRATERNALE, ALESSANDRA;PAOLETTI, MARIA FILOMENA;CASABIANCA, ANNA;ORLANDI, CHIARA;MAGNANI, MAURO
2009-01-01

Abstract

PNAPR2 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 PNAPR2 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. PNAPR2, either added to the medium at a concentration of 100 μM or loaded into RBC at about 40 μM, inhibited p24 production ~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 PNAPR2, both when given free and encapsulated into RBC; (2) the antiviral effect obtained by free PNAPR2 at a concentration of 100 μM is achievable by encapsulating it into RBC at a concentration of 40 μM, suggesting that RBC can be used as a delivery system to increase the antisense effect of PNAPR2.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11576/2504181
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