The nucleocapsid (NC) protein plays many roles in the life cycle of human immunodeficiency virus type-1 (HIV-1). Previously we selected the NC binding RNA aptamers from diverse forms of RNA libraries. Here we used one of the RNA aptamers to the NC protein. N70-13. and tested its effect on NC protein in vitro and in cells. The high affinity RNA aptamer completely abolished NC binding to the stable transactivation response hairpin and psi RNA stem-loops of HIV-1 RNA. When it was expressed in cells as an intramer it inhibited the packaging of viral genomic RNA and therefore promises to be an effective anti-HIV therapeutic tool. (C) 2004 Elsevier Inc. All rights reserved.