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  • Title: Anti-proliferative effects of unmodified antisense oligodeoxynucleotides targeted against c-raf mRNA: use of poly (lysine/serine) copolymers or cationic lipopolyamines.
    Author: Aoki Y, Kawa S, Karasawa Y, Horiuchi A, Kiyosawa K.
    Journal: Clin Exp Pharmacol Physiol; 1998 Sep; 25(9):702-5. PubMed ID: 9750959.
    Abstract:
    1. It is now known that nuclease-resistant phosphorothioate antisense oligodeoxynucleotides (ODN) have some actions that are unrelated to antisense mechanisms. In the present study we assessed the anti-proliferative effects of phosphorothioate (PS) and phosphodiester (PO; unmodified) antisense ODN targeted against c-raf mRNA on pancreatic cancer cells in vitro, using poly (lysine/serine) copolymers conjugated with polyethylene glycol (PLSP) or cationic lipopolyamines (Transfectam) as carriers. 2. The anti-proliferative effect of the PO antisense ODN was significantly (P < 0.05) greater than that of the PS ODN, either complexed with PLSP (2 mumol/L ODN) or the Transfectam (0.5 mumol/L ODN). However, the effect of the PS or PO antisense ODN was not dependent on the antisense sequence. The c-raf mRNA levels, assessed by reverse transcription-polymerase chain reaction, were obviously reduced by both PO and PS antisense ODN compared with mismatched ODN when complexed with the Transfectam (1 mumol/L ODN). 3. Although the anti-proliferative effects were mainly unrelated to antisense mechanisms, unmodified antisense ODN complexed with some carriers could be used as anti-tumour agents considering that synthetic carriers can be modified to improve functions, such as delivery.
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