Protein Engineering of Factor IX

The ability to produce large quantities of purified recombinant proteins
has expanded the field of protein therapeutics to the point where many
of the most widely used drugs worldwide are now engineered proteins.
Purified Factor IX protein, which is used as a preventative therapy for
uncontrolled bleeding in patients who have hemophilia B, is an example
of a therapeutic protein. However, because of the instability of purified
human Factor IX protein, patients who have hemophilia B require weekly
intravenous infusions in a clinical setting. More recently, protein engineering
has been used to improve the stability, activity, and bioavailability
of purified Factor IX protein by introducing specific codon changes in
the Factor IX gene to alter the amino acid sequence at key positions. One
of these recombinant Factor IX proteins is dalcinonacog alfa, which has
been shown in human clinical trials to be effective for use as an at-home
injectable drug, as is insulin for people who have diabetes. Protein production
and purification is the cornerstone of protein therapeutics.