Meeting report : antisense oligonucleotides

The use of antisense oligonucleotides as a therapeutic tool in modulating gene expression represents a newly established strategy for treating diseases. Such oligomers may be designed to complement a region of a specific gene or messenger RNA. Using this approach, oligonucleotides can serve as a potential block of transcription or translation through sequence-specific hybridization with targeted genetic segments. In the Fourth Meeting of the Italian Society of Experimental Hematology "Discutiamone Insieme", authors reported the use of in vitro synthesized oligonucleotides to inhibit normal and chimeric gene expression of bcl-2 in normal and neoplastic cell lines, respectively, that carry the t(14;18) translocation. The roles of c-myb and B-myb in the control of the proliferation and differentiation of normal hematopoietic cell lines have been investigated by selective inhibition of the expression of specific transcripts. To get some insight into the correlation between proliferation and differentation in myeloid cells, some authors studied and reported the differentation potential of G1-arrested cells obtained by a specific oligodeoxynucleotide complementary to the 5' region of the c-myb mRNA. The use of anti-P53 antisense oligos in the modulation of the growth of normal and neoplastic bone marrow progenitors was presented and confirmed the pivotal role of this gene in cell cycle control. The role of abl gene expression in normal and chronic myelogenous leukemia (CML) cells is not yet completely understood. Selective inhibition of this proto-oncogene and of the abl-bcr oncogene have been achieved by using of c-abl sequence specific antisense oligonucleotides; this approach sheds new light on the function of this gene in CML. Furthermore, recent reports describe direct DNA interaction with oligonucleotides resulting in intermolecular triple helix (triplex) formation, or the use of a full antisense message in the inhibition of gene expression. The multidrug resistance (MDR1) gene was targeted by sequence specific oligonucleotides capable of forming a triplex helix with genomic DNA. The level of expression of the MDR1 gene was reduced in presence of these oligonucleotides, showing the usefulness of this new approach in the modulation of gene transcription. Finally, the use of an antisense messenger RNA (asRNA) strategy to study UL44 gene function (DNA polymerase accessory protein) in human cytomegalovirus (HCMV) was reported. Strong viral inhibition was been observed at various times after infection a sensitive cell line. The papers presented at this meeting, demonstrate the multiplicity of ways antisense RNA technology can be utilized for studying gene functions and offer a model for future specific gene therapy in normal, neoplastic and infective hematological diseases.