Oligonucleotides first-generation

Parenteral administration has been the preferred route because it allows complete systemic availability. Non-parenteral administration of antisense oligonucleotides is only made possible with the aid of novel formulations intended to overcome barriers to absorption (see Chapter 10). Similar to first-generation anti-sense oligonucleotides (ASOs), the pharmacokinetics of2 -MOE partially modified ASOs are characterized by ... 

ASOs have been administered by many of these routes - generally with marked success even with the shorter half-life first-generation oligonucleotide chemistries. Besides Vitravene for CMV retinitis, first-generation ASOs have also been administered locally for ulcerative colitis (rectal), human papillomavirus (HPV) infec-... 

Fig. 8.4. First-generation generalized structures of natural DNA (phosphodiester) and three antisense oligonucleotide derivatives tested as antisense drugs. (Adapted from Agrawal S, Iyer RP. Perspectives in antisense therapeutics. Pharmacol Ther 1997 76 151-160 with permission.)...

Some oligonucleotide modifications, however, do support RNase H activity. One of the first generation of antisense drugs developed, phosphorothioates (shown in Figure 1), falls in this category 14). While this... 

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