Ah. Wang et Jh. Wang, Effective treatment of murine leukemia with antisense poly-2 '-O-(2,4-dinitrophenyl)-oligoribonucleotides, ANTISENSE N, 9(1), 1999, pp. 43-51
Two antisense poly-2'-O-(2,4-dinitrophenyl) -oligoribonucleotides (poly-DNP
-RNA) have been synthesized and tested for the treatment of murine leukemia
. Compound I was designed as a bifunctional inhibitor of either the reverse
transcriptase (RT) activity or viral envelope synthesis in Moloney murine
leukemia virus (MMLV), Compound II was designed as a trifunctional inhibito
r of either RT activity or envelope synthesis or protease synthesis in MMLV
, Administration of either I or II to MMLV-infected mice for 3 weeks decrea
sed viremia gradually to below the level detectable by RT-PCR, Viremia did
not reappear 8 weeks after termination of treatment, when most of the mice
were killed for autopsy. All infected but untreated mice died within 6 mont
hs with enlarged spleens that exhibited abnormal histologic signs and were
found by PCR to contain the DNA of integrated viral genome, The infected mi
ce that had been treated subsequently with adequate dosage of compound I or
II had normal spleens, continued to live on, and had no integrated MMLV ge
nome in their spleen and bone marrow samples, The effective i.p, dosage (ED
50) for compounds I and II are 0.25 and 0.1 mg/kg, respectively, which are
200-fold to 500-fold lower than that of the monofunctional RT inhibitor pol
y-DNP-oligo A. The estimated effective oral dosage of compound II is 1.2 mg
/kg.