Biomedical Engineering Reference
In-Depth Information
fi ltration or SDS-PAGE) indicates that the approved PEGylated products consist predominantly of
monoPEGylated interferon molecules, with small amounts of both free and diPEGylated species
also being present.
The intrinsic biological activity of PEGylated and non-PEGylated interferons is essentially
the same. The PEGylated product, however, displays a signifi cantly prolonged plasma half-life
(13-25 h, compared with 4 h for unpegylated species). The prolonged half-life appears to be due
mainly to slower elimination of the molecule, although PEGylation also appears to decrease sys-
temic absorption from the site of injection following subcutaneous administration, as discussed
in Chapter 4.
Infergen (interferon alfacon-1 or consensus interferon) is an engineered interferon recently ap-
proved for the treatment of hepatitis C (Table 8.8). The development of infergen entailed initial
sequence comparisons between a range of IFN-αs. The product's amino acid sequence refl ects
the most frequently occurring amino acid residue in each corresponding position of these native
interferons. A DNA sequence coding for the product was synthesized and inserted into
E. coli
.
The recombinant product accumulates intracellularly as inclusion bodies.
Large-scale manufacture entails an initial fermentation step. After harvest, the
E. coli
cells
are homogenized and the inclusion bodies recovered via centrifugation. After solubilization and
re-folding, the interferon is purifi ed to homogeneity by a combination of chromatographic steps.
The fi nal product is formulated in the presence of a phosphate butter and sodium chloride. It is
presented as a 30 µg ml
1
solution in glass vials and displays a shelf life of 24 months when stored
at 2-8
C. When compared on a mass basis, the synthetic interferon displays higher antiviral, anti-
proliferative and cytokine-inducing activity than do native type I interferons.
Ongoing clinical trials continue to assess the effi cacy of recombinant interferon preparations in
treating a variety of cancers. Some trials suggest that treatments are most effective when adminis-
tered in the early stages of cancer development. rhIFN-
s have also proven effective in the treat-
ment of various viral conditions, most notably viral hepatitis. Hepatitis refers to an infl ammation
of the liver. It may be induced by toxic substances, immunological abnormalities, or by viruses
(infectious hepatitis). The main viral causative agents are:
α
•
hepatitis A virus (hepatitis A);
•
hepatitis B virus (hepatitis B, i.e. classical serum hepatitis);
•
hepatitis C virus (hepatitis C, formerly known as classical non-A, non-B hepatitis);
•
hepatitis D virus (hepatitis D, i.e. delta hepatitis);
•
hepatitis E virus (hepatitis E, i.e. endemic non-A, non-B hepatitis);
•
hepatitis GB agent.
This disease may be acute (rapid onset, often accompanied by severe symptoms, but of brief dura-
tion) or chronic (very long duration).
Hepatitis A is common, particularly in areas of poor sanitation, and is transmitted by food or
drink contaminated by a sufferer/carrier. Clinical symptoms include jaundice and are usually
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