Immunogenicity of Aptamers

Studies in rodents have evaluated the immunogenic potential of aptamers (Vater and Klussmann, 2003; Wlotzka et al., 2002). Five ligands (one with 2'-deoxy nucleosides, one with 2'-NH2-substituted pyrimidines, and three with 2'-fluoro-sub-stituted pyrimidines with and without PEG) have been tested. The aptamers were administered intradermally, subcutaneously, or intravenously (depending upon the design in each study) in buffered saline each week for 4-8 weeks. Plasma was taken from the animals weekly after the second injection of aptamer. No anti-aptamer antibody could be detected in any of the animals in the treated groups at any time point regardless of whether the oligonucleotide was administered in saline alone or in saline plus Freund's or Ribi adjuvant (intradermally or subcutaneously). These data indicate that aptamers have essentially no immuno-genic potential in rodents.

The immunogenic potential of aptamers has also been studied in both primates and humans. No antigenic response was detected in studies of single- and multiple-dose intravitreal injections of the anti-VEGF aptamer Macugen/EYE001 in Rhesus monkeys. Likewise, no antigenic response was observed in the Phase I clinical trial of Macugen for AMD (Eyetech Study Group, 2002).

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