Zidovudine

Zidovudine pretreatment has potent anti-HIV-1 activity in the newly infected T and monocytic cells but not in chronically infected cells. ^[1] Inhibition of reverse transcription by Zidovudine decreases p24 antigen levels modestly, decreased HIV-1 gag by 19-fold, and inhibits detection of 2-LTR HIV-1 DNA. ^[2] Zidovudine and dideoxynucleosides deplete wild-type mitochondrial DNA levels and increase deletedmitochondrial DNA levels in cultured Kearns-Sayre syndrome fibroblasts. ^[3] Zidovudine (AZT, 0.1-50 mM) has a concentration dependent suppressive effect on the growth of granulocyte-monocyte colony forming unit (CFU-GM) derived colonies. Zidovudine exposure also induces a concentration dependent suppressive effect (35-90%) on GM-CSF receptor type alpha (GM-CSFR alpha) gene expression. Zidovudine causes a much lower decrease (15-22%) on the IL-3 receptor type alpha (IL-3R alpha) message level, and has an insignificant effect on glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and c-myc message levels. ^[4] Zidovudine causes a concentration-dependent inhibition in the levels of the mRNA of Epo receptors and c-fos, whereas the level of c-myc mRNA is unaffected. Zidovudine also inhibits protein kinase C (PKC) activity in a concentration- and time-dependent manner, causing 50% inhibition at 10 mM within 3 hours. Zidovudine-induced down-regulation of Epo receptors and c-fos expression coupled with inhibition of Epo receptor-mediated signal transduction through PKC are significant contributory factors to AZT-induced erythroid toxicity. ^[5] Zidovudine could decrease the HDR efficiency. It decrease CRISPR-mediated sequence-specific genome knockin events while increases knockout efficiency^[6] .