Many neurons of the central nervous system display multiple high voltage-activated Ca2+ currents, pharmacologically classified as L-, N-, P-, Q-, and R-type. Of these current types, the R-type is the least understood. The leading candidate for the molecular correlate of R-type currents in cerebellar granule cells is the alpha1E subunit, which yields Ca2+ currents very similar to the R-type when...

We have used a ribonuclease protection assay to investigate RNase H cleavage of HIV-1 mRNA mediated by phosphorothioate antisense oligonucleotides complementary to the gag region of the HIV-1 genome in vitro. Cell lysate experiments in H9 and U937 cells chronically infected with HIV-1 IIIB showed RNase H cleavage of unspliced gag message but no cleavage of spliced message which did not contain ...

Defining target sites for antisense oligonucleotides in highly structured RNA is a non-trivial exercise that has received much attention. Here we describe a novel and simple method to generate a library composed of all 20mer oligoribonucleotides that are sense- and antisense to any given sequence or genome and apply the method to the highly structured HIV-1 leader RNA. Oligoribonucleotides that...

The impact of human papilloma virus (HPV16) E7 proteins and retinoblastoma (RB) antisense oligonucleotides upon mitogen-activated protein kinase (MAPK)-mediated inhibition of DNA synthesis via p21(Cip-1/WAF1/MDA6) (p21) was determined in primary hepatocytes. Prolonged activation of the MAPK pathway in p21(+/+) or p21(-/-) hepatocytes caused a large decrease and increase, respectively, in DNA sy...

Human Papillomaviruses (HPVs) are small double-stranded DNA viruses that infect the cutaneous or mucosal epithelium. The high-risk genital HPVs are associated with squamous intraepithelial lesions of the anogenital region that can progress to cancer. Cervical cancer is the third leading cause of cancer death in women worldwide, yet there are no specific therapeutic treatments for HPV-associated...

The specificity of antisense oligonucleotides targeted to the mRNA breakpoint region of the Bcr-Abl oncogene, found in leukaemic cells from patients with chronic myeloid leukaemia, remains controversial due to non-specific effects. To prevent protein binding of oligonucleotides we designed and tested a methylphosphonate oligonucleotide with an attached 3' soluble phosphodiester tail. Growth of ...

Malignant glioma, the most common human brain cancer, is almost uniformly fatal. Median survival is less than one year. The principal strategies of gene therapy for treatment of gliomas, including antisense approach, have been proposed comming from 1990s [1, 2, 3, 4]. The antisense oligonucleotides become the important tool of anti-cancer approach [5, 6]. The "discovery" of antisense approach w...