Oligonucleotide uptake in human hematopoietic cells is increased in leukemia and is related to cellular activation.
The use of antisense oligonucleotides as tools for modulating gene expression represents a novel strategy for designing drugs to treat a variety of diseases. Several factors, including cellular uptake and internalization of the oligonucleotides, are important parameters in determining the effectiveness of antisense agents such as therapeutic drugs. We have studied oligonucleotides uptake in normal and leukemic human hematopoietic cells, such as peripheral blood, bone marrow (BM), and HL-60 cell line; and have found that, in normal human blood and BM, myeloid cells and B cells preferably took up more oligonucleotides than T cells. There was no marked difference in oligonucleotide uptake between CD4+ helper T cells and CD8+ cytolytic T cells. Leukemic cells had greater oligonucleotide uptake than their normal counterparts. Furthermore, oligonucleotide uptake was closely related to cell activation status and can be modulated by growth factors or inhibitors. These studies provide a basis for using oligonucleotides as therapeutic drugs both in vitro and in vivo.
Zhao
Q
Q
Veterans Affairs Medical Center, Iowa City, USA.
Song
X
X
Waldschmidt
T
T
Fisher
E
E
Krieg
A M
AM
D001483:Base Sequence; D001853:Bone Marrow / Q000378:metabolism; D002455:Cell Division; D018922:HL-60 Cells / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000378:metabolism; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D016376:Oligonucleotides, Antisense