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Box 1 | Functional classification of protein therapeutics
Protein therapeutics in the tables in this article are organized by function and therapeutic
application. The numbers of therapeutics per group reflect the relative difficulty associated with
drug development across the various classes of protein therapeutics. Every effort has been made to
include in these tables all US Food and Drug Administration (FDA)-approved Group I and Group II
protein-based therapies. Groups III and IV present selected examples that highlight the use of
proteins in vaccines and diagnostic agents.
Perspectives
Table 1 | Protein therapeutics replacing a protein that is deficient or abnormal (Group Ia)*
Therapeutic
Trade name
Function
Insulin1620
Humulin, Novolin
Insulin human
inhalation146149
Exubera
Diabetes mellitus
Insulin aspart150;
insulin glulisine151;
Insulin lispro150
Novolog (aspart),
Apidra (glulisine),
Humalog (lispro)
Diabetes mellitus
Diabetes mellitus
Insulin detemir152;
Insulin glargine150
Levemir (detemir),
Lantus (glargine)
Diabetes mellitus
Insulin zinc
extended150
Lente, Ultralente
Diabetes mellitus
Pramlintide
acetate153
Symlin
Growth
hormone (GH),
somatotropin133137
Genotropin, Humatrope,
Norditropin, NorIVitropin,
Nutropin, Omnitrope,
Protropin, Siazen,
Serostim, Valtropin
Mecasermin154
Increlex
Mecasermin
rinfabate155
IPlex
Bioclate, Helixate,
Kogenate, Recombinate,
ReFacto
Coagulation factor
Haemophilia A
Factor IX29,30,141,142
Benefix
Coagulation factor
Haemophilia B
Antithrombin III
(AT-III)143,144
Thrombate III
Protein C
concentrate145
Ceprotin
*Continued in TABLE 2. Protein therapeutics derive their specificity and function from their structure. Molecules ranging from large and complex enzymes to short peptide
sequences have specific biological activity due to their amino-acid-based secondary and tertiary structure. For example, somatostatin is active as either a 14 or 28 amino-acid
peptide, and its even shorter synthetic analogues share a characteristic hairpin-loop structure that defines their specificity and biological activity. Some very short peptide
therapeutics are better thought of as small-molecule drugs, as they lack secondary and tertiary structures that define their biological activity. For this reason, therapeutics such as
glatiramer acetate (a four amino-acid peptide consisting of acetate with lGlu, lAla, lTyr and lLys) are not addressed in this article. Protein therapeutics are recombinant unless
otherwise stated. Also classed in Group Ib. Non-recombinant.
Perspectives
cystic fibrosis, a common lethal genetic
disorder. In this disease, defects in the
chloride channel encoded by the CFTR gene
lead to abnormally thick secretions, which
can (among other effects) block pancreatic
enzymes from travelling down the pancreatic
duct into the duodenum31. This prevents
food from being properly digested and
results in malnutrition. Patients with cystic
fibrosis are often treated with a combination
of pancreatic enzymes isolated from pigs
including lipases, amylases and proteases
that allow the digestion of lipids,
sugars and proteins. Patients who have had
their pancreas removed or who suffer from
chronic pancreatitis can also benefit from
this therapy5,6. Other striking examples
include various diseases caused by metabolic
enzyme deficiencies, such as Gauchers
disease as mentioned above, mucopolysaccharidosis, Fabry disease and others.
Additional protein therapies that replace a
particular activity are listed in TABLES1,2.
It may sometimes be desirable to enhance
the magnitude or timing of a particular normal protein activity, and protein therapeutics
that we have classified in Group Ib are
administered to achieve this. Such protein
therapeutics have been successful in treating
haematopoietic defects; the most prominent
example is recombinant erythropoietin,
a protein hormone secreted by the kidney
that stimulates erythrocyte production in
the bone marrow31. In patients with chemotherapy-induced anaemia or myelodysplastic
syndrome, recombinant erythropoietin is
used to increase erythrocyte production
and thereby ameliorate the anaemia. In
patients with renal failure, whose levels of
endogenous erythropoietin are below normal, recombinant protein is administered to
correct this deficiency3236. Another example
is provided by the treatment of neutropaenic
patients with granulocyte- or granulocytemonocyte colony stimulating factor (G-CSF
or GMCSF, respectively)36,37, which stimulate an increase in the number of neutrophils
produced by the bone marrow to allow these
patients to better combat microbial infections. Similarly, thrombocytopaenic patients
can be treated with interleukin 11 (IL11)38,
which increases platelet production and
thereby prevents bleeding complications.
Invitro fertilization (IVF) is another
area in which Group Ib proteins are applied.
Increased levels of follicle-stimulating hormone (FSH) are normally produced by the
anterior pituitary gland just before ovulation.
These high levels of FSH can be enhanced by
treatment with recombinant FSH, leading to
maturation of an increased number of follicles
Perspectives
Table 2 | Protein therapeutics replacing a protein that is deficient or abnormal (Group Ia)*
Therapeutic
Trade name
Function
Cerezyme
Gauchers disease
-Glucocerebrosidase23,25,156
Gauchers disease
Alglucosidase-157
Myozyme
Laronidase158160
(-l-iduronidase)
Aldurazyme
Idursulphase161
(Iduronate-2sulphatase)
Elaprase
Mucopolysaccharidosis II (Hunter
syndrome)
Galsulphase162
Naglazyme
Mucopolysaccharidosis VI
Agalsidase-163,164
(human
-galactosidase A)
Fabrazyme
Aralast, Prolastin
Lactase26
Lactaid
Immunodeficiencies
Adenosine
deaminase166
(pegademase
bovine, PEG-ADA)
Adagen
Pooled
immunoglobulins167
Octagam
Primary immunodeficiencies
Albumarc, Albumin,
Albuminar, AlbuRx,
Albutein, Flexbumin,
Buminate, Plasbumin
Other
Human albumin168
*Continued from TABLE 1. Protein therapeutics are recombinant unless otherwise stated. Non-recombinant.
Perspectives
Table 3 | Protein therapeutics augmenting an existing pathway (Group Ib)*
Therapeutic
Trade name
Function
Erythropoietin,
Epoetin-3236,169,170
Epogen,
Procrit
Stimulates erythropoiesis
Darbepoetin-14
Aranesp
Filgrastim36, 37
(granulocyte colony stimulating
factor; G-CSF)
Neupogen
Pegfilgrastim171 (Peg-G-CSF)
Neulasta
Leukine
Oprelvekin38
(interleukin11; IL11)
Neumega
Human follicle-stimulating
hormone (FSH)39,40
Gonal-F,
Follistim
Augments ovulation
Assisted reproduction
Ovidrel
Assisted reproduction
Lutropin-172
Luveris
Type I alpha-interferon,
interferon alfacon 1, consensus
interferon173178
Infergen
Interferon-2a (IFN2a)179183
Roferon-A
PegInterferon-2a184186
Pegasys
Interferon-2b (IFN2b)187189
Intron A
PegInterferon-2b190
Peg-Intron
Interferon-n3 (IFNn3)191,192
Alferon N
Interferon-1a (rIFN-)178,193196
Avonex,
Rebif
Multiple sclerosis
Interferon-1b (rIFN-)197199
Betaseron
Multiple sclerosis
Interferon-1b (IFN)200204
Actimmune
Aldesleukin205208
(interleukin 2 (IL2), epidermal
thymocyte activating factor;
ETAF)
Proleukin
Haematopoiesis
Fertility
Immunoregulation
*Continued in TABLE 4. Protein therapeutics are recombinant unless otherwise stated. Non-recombinant.
www.nature.com/reviews/drugdisc
2008 Nature Publishing Group
Perspectives
Table 4 | Protein therapeutics augmenting an existing pathway (Group Ib)*
Therapeutic
Trade name
Function
Alteplase4246
(tissue plasminogen
activator; tPA)
Activase
Reteplase
(deletion mutein of tPA)47,48
Retavase
Tenecteplase49,50
TNKase
Urokinase209,210
Abbokinase
Pulmonary embolism
Factor VIIa51,52
NovoSeven
Drotrecogin-53,54
(activated protein C)
Xigris
Salmon calcitonin211,212
Fortical,
||
Miacalcin
Postmenopausal osteoporosis
Teriparatide213216
(human parathyroid
hormone residues 134)
Forteo
Severe osteoporosis
Byetta
Incretin mimetic with actions similar to glucagonlike peptide 1 (GLP1); increases glucose-dependent
insulin secretion, suppresses glucagon secretion,
slows gastric emptying, decreases appetite (first
identified in saliva of the Gila monster Heloderma
suspectum)
||
Octreotide218,219
Sandostatin
Dibotermin-220,221
(recombinant human bone
morphogenic protein 2;
rhBMP2)
Infuse
Mechanism unknown
Osteogenic
protein 1
Mechanism unknown
||
Histrelin acetate223,224
(gonadotropin releasing
hormone; GnRH)
Supprelin LA,
Vantas
Palifermin225
(keratinocyte growth factor;
KGF)
Kepivance
Becaplermin226228
(platelet-derived growth
factor; PDGF)
Regranex
Trypsin229
Granulex
Proteolysis
Nesiritide230, 231
Natrecor
Endocrine disorders
Exenatide217
||
Growth regulation
Other
*Continued from TABLE 3. Protein therapeutics are recombinant unless otherwise stated. Also classed in Group Ic. Non-recombinant. ||Synthetic.
Perspectives
Some Group IIa proteins are used to treat
infectious diseases. Patients at high-risk for
severe respiratory syncytial virus (RSV)
infection, one of the leading causes of hospital
admissions for paediatric respiratory
illness, are given a recombinant monoclonal
Therapeutic
Trade name
Function
Botox
*Botulinum toxin
type B233,234
Myoblock
*Collagenase56,57
Collagenase,
Santyl
Human deoxyribonuclease I,
dornase-58
Pulmozyme
*Hyaluronidase
(bovine, ovine)235
Amphadase
Catalyses the hydrolysis of hyaluronic acid to
(bovine), Hydase increase tissue permeability and allow faster drug
(bovine), Vitrase absorption
(ovine)
Hyaluronidase
(recombinant
human)236
Hylenex
*Papain55
Accuzyme,
Panafil
ELSPAR
*Peg-asparaginase59
Oncaspar
Rasburicase237
Elitek
Refludan
Bivalirudin238,239
Angiomax
*Streptokinase6365,240
Streptase
*Anistreplase241,242
(anisoylated
plasminogen
streptokinase activator
complex; APSAC)
Eminase
Protein therapeutics are recombinant unless otherwise stated. *Non-recombinant. Synthetic. FVC, forced vital capacity; SNAP25, synaptosomal-associated protein, 25 kDa;
SNARE, soluble N-ethylmaleimide-sensitive factor attachment protein receptor.
www.nature.com/reviews/drugdisc
2008 Nature Publishing Group
Perspectives
Another area in which Group IIa antibodies have been successful is oncology.
For example, rituximab is a human/mouse
chimeric monoclonal antibody that binds to
CD20, a transmembrane protein expressed on
>90% of Bcell non-Hodgkins lymphomas,
and targets the cells for destruction by the
bodys immune system7981. Although rituximab is most often used in combination with
anthracycline-based chemotherapy, it is one
of the few monoclonal antibody anticancer
therapies that is approved as a monotherapy.
Cetuximab is a monoclonal antibody that is
used to treat colorectal cancer and head and
neck cancer; this monoclonal antibody binds
epidermal growth factor receptor (EGFR) and
impairs cancer cell growth and proliferation82.
Other recently developed Group IIa protein
therapeutics are listed in TABLES6,7, and
many more protein therapeutics utilizing the
exquisite specificity of monoclonal antibodies
are in development, especially for cancer and
inflammatory diseases.
Many important processes are modulated
by cell-surface receptors that are activated
upon binding of their cognate ligands15.
By binding to such receptors, targeted protein therapeutics may activate cell signalling
pathways and profoundly affect cell function. Outcomes may range from cell death
(through the induction of apoptosis), to
downregulation of cell division to increased
cell proliferation. Although it has been diffi
cult to prove that a particular target-binding
protein mediates an invivo effect through the
modulation of a particular signalling pathway, invitro evidence suggests that this type
of modulation is involved in the mechanism
of action of certain therapeutic proteins.
For example, the treatment of certain breast
cancers, in which the malignant cells express
the HER2/Neu (also known as ERBB2) cell
surface receptor, is enhanced by the addition
of trastuzumab (an anti-HER2/Neu monoclonal antibody) to the therapeutic regimen83.
Although trastuzumab contains an Fc region
that facilitates antibody-dependent cellular
cytotoxicity mediated by natural killer cells, it
seems unlikely that this is trastuzumabs only
mechanism of action. Other monoclonal
antibodies, with similar Fc regions and abilities to target breast cancer cells, have failed to
show efficacy invivo. Trastuzumab, however,
has been shown invitro to induce intracellu
lar signalling events that control the growth
of breast cancer cells. It is therefore likely
that a combination of mechanisms accounts
for the therapeutic activity of trastuzumab,
including inhibition of the phosphatidyl
inositol 3-kinase (PI3K) pathway, inhibition
of angiogenesis and inhibition of HER2
Perspectives
vaccine against human papillomavirus
(HPV) combines the major capsid proteins
from four HPV strains that commonly
cause genital warts (strains 6 and 11) and
cervical cancer (strains 16 and 18)97.
administration of large amounts of this selfprotein causes the bodys immune system to
develop tolerance to that protein by eliminating or deactivating cells that react against
the self-protein. Proteins that we have
Table 6 | Protein therapeutics that interfere with a molecule or organism (Group IIa)*
Therapeutic
Bevacizumab243246
Avastin
Cetuximab140
Erbitux
Panitumumab
Vectibix
Alemtuzumab248
Campath
Trastuzumab84
Herceptin
Breast cancer
Abatacept252
Orencia
Anakinra253255
Antril,
Kineret
Adalimumab256,257
Humira
Etanercept6870
Enbrel
Infliximab7173
Remicade
Chimeric mAb that binds and neutralizes TNF, preventing Rheumatoid arthritis, Crohns disease, ankylosing
spondylitis, psoriatic arthritis, plaque psoriasis
induction of pro-inflammatory cytokines, changes in
endothelial permeability, activation of eosinophils and
neutrophils, induction of acute phase reactants, and
enzyme elaboration by synoviocytes and/or chondrocytes
Alefacept258,259
Amevive
Efalizumab260,261
Raptiva
Natalizumab262
Tysabri
Eculizumab263,264
Soliris
Cancer
247
Immunoregulation
*Continued in TABLE 7. Protein therapeutics are all recombinant. CHOP, cyclophosphamide, hydroxydaunorubicin, oncovin (vincristine), prednisone/prednisolone;
CTLA4, cytotoxicT-lymphocyte-associated antigen 4; CVP, cyclophosphamide, vincristine, prednisone; EGFR, epidermal growth factor receptor; LFA3, leukocyte functionassociated antigen 3; mAb, monoclonal antibody; MadCAM1, mucosal addressin cell adhesion molecule 1; TNF, tumour necrosis factor; VCAM1, vascular cell adhesion
molecule-1; VEGFA, vascular endothelial growth factor A.
www.nature.com/reviews/drugdisc
2008 Nature Publishing Group
Perspectives
classified in Group IIIb are used to treat
patients with disorders that arise from
this type of autoimmune phenomenon.
Immunological acceptance of a fetus during
pregnancy represents a special situation
Table 7 | Protein therapeutics that interfere with a molecule or organism (Group IIa)*
Therapeutic
Trade name
Function
Transplantation
Antithymocyte
globulin
(rabbit)265267
Basiliximab268
Simulect
Daclizumab269
Zenapax
MuromonabCD3270272
Orthoclone,
OKT3
Omalizumab273275 Xolair
Palivizumab74,75
Somavert
Acromegaly
Crotalidae
polyvalent
immune Fab
(ovine)281,282
Crofab
Digoxin immune
serum Fab
(ovine)283,284
Digifab
Digoxin toxicity
Ranibizumab285
Lucentis
Pulmonary disorders
Synagis
Infectious diseases
Enfuvirtide7678
Fuzeon
ReoPro
Endocrine disorders
Pegvisomant279,280
Other||
*Continued from TABLE 6. Protein therapeutics are recombinant unless otherwise stated. Non-recombinant. Purified immune globulins can also be used to mitigate the acute
affects of exposure to an infectious agent. Human immune globulins targeting botulism, cytomegalovirus, hepatitis B, rabies, tetanus, and vaccinia have been approved by the
FDA. ||Two additional antivenins have been approved by the FDA: Antivenin immune globulin (equine) Latrodectus mactans (black widow spider); Antivenin immune globulin
(equine) Micrurus fulvius (North American coral snake). Fab, fragment antigen-binding; IgE/G/G1, immunoglobulin E/G/G1; IL2, interleukin 2; mAb, monoclonal antibody;
PEG, polyethylene glycol.
Perspectives
Table 8 | Protein therapeutics that deliver other compounds or proteins (Group IIb)
Therapeutic
Denileukin
diftitox89,90
Ontak
Persistent or recurrent
cutaneous T-cell lymphoma
whose malignant cells express
the CD25 component of the
IL2 receptor
*Ibritumomab
tiuxetan88
Zevalin
Relapsed or refractory
low-grade, follicular, or
transformed B-cell nonHodgkins lymphoma (NHL),
including rituximab-refractory
follicular NHL
Gemtuzumab
ozogamicin86,87
Mylotarg
Humanized anti-CD33
IgG4k mAb conjugated
to calicheamicin,
a small-molecule
chemotherapeutic agent
Tositumomab is a mAb
that binds CD20 surface
antigen and stimulates
apoptosis. Tositumomab
coupled to radioactive
iodine-131 binds CD20
surface antigen and
delivers cytotoxic
radiation
*Tositumomab
Bexxar,
and 131IBexxar I-131
tositumomab286,287
Protein therapeutics are all recombinant. *Also classed in Group IIa. IL2, interleukin 2; mAb, monoclonal antibody.
and pregnancy loss do not occur in subsequent pregnancies, even when the new fetus
carries the Rh antigens98.
Proteins that we have classified in Group
IIIc could be used as therapeutic anticancer
vaccines. Although there are currently no
FDA-approved recombinant anticancer
vaccines, there are promising clinical trials
that use patient-specific cancer vaccines. For
example, a vaccine for Bcell non-Hodgkins
lymphoma uses transgenic tobacco plants
(Nicotiana benthamiana)99. Each patient
with this type of lymphoma has a malignant
proliferation of an antibody-producing Bcell
that displays a unique antibody on its surface.
By subcloning the idiotype region of this
tumour-specific antibody and expressing the
region recombinantly in tobacco plants, a
tumour-specific antigen is produced that can
be used to vaccinate a patient. This process
requires only 68 weeks from biopsy of the
lymphoma to a ready-to-use, patient-specific
vaccine. As the genomes of infectious organisms and the nature of autoimmune diseases
and cancer are more fully elucidated, more
recombinant proteins will undoubtedly be
developed for use as vaccines.
Group IV: protein diagnostics
Proteins that we have classified in Group
IV are not used to treat disease, but purified
and recombinant proteins used for medical
Perspectives
First, protein solubility, route of administration, distribution and stability are all
factors that can hinder the successful application of a protein therapy114,115. Proteins
are large molecules with both hydrophilic
and hydrophobic properties that can make
entry into cells and other compartments
of the body difficult, and the half-life of
a therapeutic protein can be drastically
affected by proteases, protein-modifying
chemicals or other clearance mechanisms.
One example of how such challenges are
being addressed is through the production of PEGylated versions of therapeutic
proteins. For example, PEG-interferon is a
modified form of interferon in which the
polymer polyethylene glycol (PEG) is added
to prolong the absorption, decrease the renal
clearance, retard the enzymatic degradation,
increase the elimination half-life and reduce
the immunogenicity of interferon15.
A second important challenge is that
the body may mount an immune response
against the therapeutic protein116. In some
cases, this immune response can neutralize
the protein and can even cause a harmful
reaction in the patient. For example, immune
responses can be generated against Group
Ia therapeutic proteins used to replace a
factor that has been missing since birth, as
illustrated by the development of antifactor
VIII antibodies (inhibitors) in patients with
severe haemophilia A who are treated with
recombinant human factor VIII117,118. More
commonly, however, immune responses are
generated against proteins of non-human
origin. Until quite recently, the widespread
clinical application of monoclonal antibodies
had been limited by the rapid induction
of immune responses against this class of
therapeutic proteins. The need for antibody
therapeutics that evade immune surveillance
and response has been a driving force in the
maturation of antibody production technology. Recombinant technology and other
advances have allowed the development
of various antibody products that are less
likely to provoke an immune response than
unmodified murine antibodies. In humanized antibodies, portions of the antibody that
are not critical for antigen-binding specificity
are replaced with human Ig sequences that
confer stability and biological activity on the
protein but do not provoke an anti-antibody
response; and fully human antibodies can be
produced using transgenic animals or phage
display technologies67,119.
The field of cancer therapeutics illustrates the pace of advances in monoclonal
antibody development. In the 1980s, most
of the monoclonal cancer therapeutics
Therapeutic
Trade name
Function
Engerix,
Non-infectious protein
Recombivax HB on surface of hepatitis
B virus
Hepatitis B vaccination
HPV vaccine97
Gardasil
Quadrivalent HPV
recombinant vaccine
(strains 6, 11, 16, 18);
contains major capsid
proteins from four
HPV strains
OspA95,96
LYMErix
Non-infectious
lipoprotein on outer
surface of Borrelia
burgdorferi
Rhophylac
Neutralizes Rh
antigens that could
otherwise elicit antiRh antibodies in an
Rh-negative individual
*Selected vaccines highlight the use of recombinant protein technology in vaccine production. Vaccines for the
following agents or diseases are currently approved by the FDA: anthrax, acellular pertussis, BCG (for childhood
TB protection), diphtheria, hepatitis A and B, human papillomavirus (HPV) types 6,11,16,18, influenza types A, B,
and H5N1, Japanese encephalitis, Lyme disease, measles, meningococcus, mumps, plague, pneumococcus, polio,
rabies, rotavirus, rubella, smallpox, tetanus, typhoid, varicella-zoster, and yellow fever (see http://www.fda.gov/
cber/vaccine/licvacc.htm).
Perspectives
may be different in large-scale production
and storage systems than in those used to
produce the protein for animal testing and
clinical trials125,126. Some have proposed
engineering host systems that co-express a
chaperone or foldase with the therapeutic
protein of interest, but these approaches
have had limited success.
Diagnostic
Trade name
Function
DPPD
*Glucagon288,289
GlucaGen
Geref
Secretin290,291
ChiRhoStim (human
peptide), SecreFlo
(porcine peptide)
Thyrogen
Capromab pendetide108
ProstaScint
Indium-111-octreotide292
OctreoScan
Satumomab pendetide293
OncoScint
Arcitumomab294,295
CEA-scan
Nofetumomab296
Verluma
Apcitide107
Acutect
Imciromab pentetate297
Myoscint
Technetium fanolesomab298
NeutroSpec
Hormones
Enzyme immunoassay,
OraQuick, Uni-Gold
Hepatitis C antigens112,113
Recombinant immuno- Detects human antibodies to hepatitis C virus Diagnosis of hepatitis C exposure
blot assay (RIBA)
Protein diagnostics are recombinant unless otherwise stated. *Also classed in Group Ib. Also classed in Group Ia. Synthetic. CEA, carcinoembryonic antigen; mAb, monoclonal
antibody; PSA, prostate-specific antigen.
www.nature.com/reviews/drugdisc
2008 Nature Publishing Group
Perspectives
engineered to secrete protein in their milk,
and transgenic chickens that lay eggs filled
with recombinant protein are anticipated
in the future129. Transgenic plants can inexpensively produce vast quantities of protein
without waste or bioreactors130, and potatoes
can be engineered to express recombinant
proteins and thereby make edible vaccines9.
Finally, by using fluid-shaking bioreactors,
microlitre-sized culture systems might be
able to predict the success of large-scale
culture systems and thereby provide substantial cost savings by focusing investment on
systems that are more likely to succeed131.
A fourth important challenge is the costs
involved in developing protein therapies.
For example, switching to recombinant
methodology from laborious purification
of placentally derived protein has allowed
the production of sufficient -glucocerebrosidase to treat Gauchers disease in many
patients. Even so, the cost of the
recombinant protein can be greater than
US$ 100,000 per patient per year132.
The example of Gauchers disease also
illustrates aspects of a fifth issue associated
with protein therapeutics: ethics (although
these ethical issues are not exclusive to
protein therapeutics). For example, the
possibility of efficacious but expensive protein
therapeutics for small but severely ill patient
populations, such as patients with Gauchers
disease, can present a dilemma with respect to
allocation of financial resources of health-care
systems132. In addition, the definition of illness or disease could be challenged by protein
therapeutics that can improve upon conditions previously viewed as variants of normal.
For example, the definition of short stature
may begin to change with the possibility of
using growth hormone to increase the height
of a child133137.
Conclusion and future directions
Medicine is approaching a new era in which
approaches to manage disease are being made
at the level of the genetic and protein information that underlies all biology, and protein
therapeutics are playing an increasingly
important role. Already, recombinant human
proteins make up the majority of FDAapproved biotechnology medicines, which
include monoclonal antibodies, natural interferons, vaccines, hormones, modified natural
enzymes and various cell therapies. The
future potential for such therapies is huge,
given the thousands of proteins produced by
the human body and the many thousands of
proteins produced by other organisms.
Furthermore, recombinant proteins not
only provide alternative (or the only)
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
Correspondence to D.E.G.
e-mail: dgolan@hms.harvard.edu
doi:10.1038/nrd2399
Published online 21 December 2007
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Acknowledgements
DATABASES
OMIM:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
Amyotrophic lateral sclerosis | cervical cancer | colorectal
cancer | cystic fibrosis | diabetes mellitus type I | diabetes
mellitus type II | Fabry disease | haemophilia A | haemophilia B |
hepatitis B | hepatitis C | inflammatory bowel disease | Kaposis
sarcoma | prostate cancer | psoriasis | rheumatoid arthritis
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