Despite major advances in redesigning and producing proteins through r
ecombinant DNA technology, many therapeutic proteins are still produce
d by extraction from biological tissues or fluids, or from nonrecombin
ant microorganisms. Modification of such proteins, to improve potency
and bioavailability and reduce immunogenicity, can only be carried out
post-translationally by chemical-derivatization methods. Genetic- and
chemical-modification methods are not mutually exclusive, however, an
d may be combined to optimize protein-engineering strategies, because
chemical modification can introduce structural changes that are not en
coded by DNA into both recombinant, and nonrecombinant proteins.