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Journal Article
Review
Pharmacokinetics, pharmacodynamics and safety of aptamers.
Advanced Drug Delivery Reviews 2018 October 13
Aptamers are synthetic molecules structured as single-stranded DNA or RNA oligonucleotides that can be designed to mimic the functional properties of monoclonal antibodies. They bind to the target molecules (typically soluble or cell-bound proteins) with high affinity (with picomolar to low nanomolar range) and specificity, and therefore can be an alternative to therapeutic antibodies or peptide ligands. This paper reviews published data regarding pharmacokinetics, pharmacodynamics and safety of aptamers from preclinical and clinical studies. Aptamers have been developed for the treatment of a variety of diseases, including cancer, macular degeneration, cardiovascular disease, diabetes and anaemia of chronic diseases. There are several preclinical studies with unmodified aptamers, but the vast majority of aptamer trials in humans have been conducted with modified aptamers, because unmodified aptamers demonstrate metabolic instability, as well as rapid renal filtration and elimination. Various strategies have been developed to improve the pharmacokinetic profile of aptamers. Aside from chemical modification of nucleotides in order to stabilize them against nuclease degradation, the main modification to extend the half-life is pegylation. Therefore, the process of pegylation as well as its benefits and possible shortcomings will briefly be discussed.
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