MODIFIED ANTISENSE OLIGODEOXYNUCLEOTIDES AGAINST THE SPLICE ACCEPTOR SITE OF TOT DO NOT INHIBIT IN-VITRO HEMATOPOIETIC COLONY GROWTH IN HIV-POSITIVE PATIENTS

The hematopoietic failure in the majority of patients with progressive HIV infection is further aggravated by virustatic agents like azidoth ymidine. As an alternative therapeutic attempt, three derivatives of a n antisense oligodeoxynucleotide (ODN) against the splice acceptor sit e of the tat gene have been shown to inhibit HIV replication in vitro. This study was aimed at examining whether these agents are toxic to t he hematopoietic progenitor cells. To this end, bone marrow cells from HIV-positive and healthy persons were depleted from adherent cells to eliminate fibroblasts. In further experiments, the cells were additio nally enriched for CD34-positive hematopoietic progenitor cells or wer e depleted from delta TCS-1-positive T lymphocytes. At concentrations of 1.25-10 mu M, the three antisense ODN did not inhibit any erythrocy te or granulocyte-monocyte colony growth from CD34-positive cells, eit her from the HIV-positive or from the HIV-negative cohort. In contrast to azidothymidine, which served as inhibitory control, a significant increase of colony growth was seen after depletion of fibroblasts, of delta TCS-1-positive cells, or without cell separation. In conclusion, the three oligodeoxynucleotides do not exert any hematotoxic effect b ut do increase colony formation from low-density bone marrow cells in vitro and could therefore be useful in future clinical studies.