Biomedical Engineering Reference
In-Depth Information
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It overcomes the problem of source availability.
Many proteins of therapeutic potential are
produced naturally in the body in minute quantities. Examples include interferons (Chapter 8),
interleukins (Chapter 9) and colony-stimulating factors (CSFs; Chapter 10). This rendered
impractical their direct extraction from native source material in quantities suffi cient to meet
likely clinical demand. Recombinant production (Chapters 3 and 5) allows the manufacture of
any protein in whatever quantity it is required.
•
It overcomes problems of product safety.
D i r e c t ex t r a c t io n of p r o d u c t f r o m s o m e n a t ive b iolog ic a l
sources has, in the past, led to the unwitting transmission of disease. Examples include the
transmission of blood-borne pathogens such as hepatitis B and C and human immunodefi ciency
virus (HIV) via infected blood products and the transmission of Creutzfeldt-Jakob disease to
persons receiving human growth hormone (GH) preparations derived from human pituitaries.
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It provides an alternative to direct extraction from inappropriate/dangerous source material.
A number of therapeutic proteins have traditionally been extracted from human urine. Follicle-
stimulating hormone (FSH), the fertility hormone, for example, is obtained from the urine of post-
menopausal women, and a related hormone, human chorionic gonadotrophin (hCG), is extracted
from the urine of pregnant women (Chapter 11). Urine is not considered a particularly desirable
source of pharmaceutical products. Although several products obtained from this source remain on
the market, recombinant forms have now also been approved. Other potential biopharmaceuticals
are produced naturally in downright dangerous sources. Ancrod, for example, is a protein displaying
anti-coagulant activity (Chapter 12) and, hence, is of potential clinical use. It is, however, produced
naturally by the Malaysian pit viper. Although retrieval by milking snake venom is possible, and
indeed may be quite an exciting procedure, recombinant production in less dangerous organisms,
such as
Escherichia coli
or
Saccharomycese cerevisiae
, would be considered preferable by most.
•
It facilitates the generation of engineered therapeutic proteins displaying some clinical advantage
over the native protein product.
Techniques such as site-directed mutagenesis facilitate the logi-
cal introduction of predefi ned changes in a protein's amino acid sequence. Such changes can be as
minimal as the insertion, deletion or alteration of a single amino acid residue, or can be more sub-
stantial (e.g. the alteration/deletion of an entire domain, or the generation of a novel hybrid protein).
Such changes can be made for a number of reasons, and several engineered products have now gained
marketing approval. An overview summary of some engineered product types now on the market is
provided in Table 1.3. These and other examples will be discussed in subsequent chapters.
Despite the undoubted advantages of recombinant production, it remains the case that many
protein-based products extracted directly from native source material remain on the market. In
certain circumstances, direct extraction of native source material can prove equally/more attrac-
tive than recombinant production. This may be for an economic reason if, for example, the protein
is produced in very large quantities by the native source and is easy to extract/purify, e.g. human
serum albumin (HSA; Chapter 12). Also, some blood factor preparations purifi ed from donor
blood actually contain several different blood factors and, hence, can be used to treat several
haemophilia patient types. Recombinant blood factor preparations, on the other hand, contain but
a single blood factor and, hence, can be used to treat only one haemophilia type (Chapter 12).
The advent of genetic engineering and monoclonal antibody technology underpinned the
establishment of literally hundreds of start-up biopharmaceutical (biotechnology) companies in
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