TRENDS IN BIOTECHDERIVED HEALTH PRODUCTS

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TRENDS IN BIOTECH-DERIVED HEALTH PRODUCTS Carol
Nonkwelo and Romilla Maharaj
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BIOTECHNOLOGY IN HEALTH

• Uses human bodys own tools i.e. proteins,
  enzymes, antibodies and other naturally produced
  substances.
• Also uses other living organisms e.g. plant and
  animal cells, viruses and yeasts for large scale
  production.
• Four primary areas in health care namely
  therapeutic agents, vaccines, diagnostics and
  gene therapy

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HEALTH State of Well-being

• Amino Acids
• Vitamins
• Vaccines

Prevention
Health
Treatment
Diagnosis

• Drugs
• Antibiotics
• Therapeutic Proteins
• Gene Therapy
• Tissue / Bone Engineering

• Molecular Diagnosis
• Monoclonal Antibodies
• Forensic Medicine

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Top Ten Biotechnologies for Improving Health in
Developing Countries

• Modified molecular technologies for affordable,
  simple diagnosis of infections diseases.
• Recombinant technologies to develop vaccines
  against infectious diseases.
• Technologies for more efficient drug and vaccine
  delivery systems.
• Technologies for environmental improvement
  (sanitation, clean water, bioremediation).
• Sequencing pathogen genomes to understand their
  biology and to identify new antimicrobials.
• Daar et.al. 2002

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• Protection against sexually transmitted diseases,
  both with and without contraceptive effect.
• Bioinformatics to identify drug targets and to
  examine pathogen-host interactions.
• Genetically modified crops with increased
  nutrients to counter specific deficiencies.
• Recombinant technology to make therapeutic
  products (for example, insulin, interferon) more
  affordable.
• Combinatorial chemistry for drug discovery.
• Daar et.al. 2002

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European Union Priorities
Promoting technological platforms for new
diagnostics, prevention therapeutics Applying
medical genomics to - diabetes, cardiovascular
rare diseases - combating resistance to
drugs - neurological diseases - human
development ageing Combating cancer Major
communicable diseases linked to poverty
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BIOLOGICAL DEFENSE TECHNOLOGIES
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Detection Diagnosis

• Rapid detection (30 min) of infectious
  diseases.
• Portable biosensors to detect pathogens in the
  air.
• Remediation technologies e.g. enzymes to
  decontaminate infectious areas.
• Molecular barriers for infectious agents.

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Therapeutics

• Antibodies to bind to anthrax toxin
• DNA or RNA based therapeutics against
  infectious diseases
• Drug delivery technologies e.g. Lozenge
  containing interferon and drug and vaccine
  patches
• Artificial skin products

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Vaccines

• Developing a third generation anthrax vaccine
• Single oral dose, rapid protection and long
  lasting

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THERAPEUTICS
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1. Scope of Pharmacogenomics
Human genome has 30-40 000 genes Produces 60-100
000 proteins Potential 3-10 000 targets for
therapeutic agents Potential for personalised
medicine
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More drugs for smaller patient populations Smaller
cohorts for clinical trials Fewer side effects
and better compliance Essential
element Routine gene testing to identify
responders those susceptible to adverse
reactions
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2. Bioinformatics
Biology
Medicine
Bioinformatics
Computer Science
Maths Physics
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• Application of tools of computation and analysis
  to capture and interpret biological data
• Contributing to functional understanding of the
  human genome
• Potential for enhanced discovery of drug targets
  and individualised therapy
• E.g. Imatinib mesylate (Gleevec) which
  interferes with the abnormal protein made in
  chronic myeloid leukemia.

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PROTEOMICS
Analysis of the total amount of proteins
expressed by a cell
Investors no longer as eager to invest in
proteomics. Want tangible therapeutic and
diagnostics products
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Genomics/Proteomics Diagnostics
Prediction growth in development of
genomics/proteomics diagnosis will surge ahead of
new therapeutics. Will take 3-4 years for these
diagnostics to be commonplace compared to 6-8
years for the therapeutics to be
developed. Focus is on mainly on infectious
diseases, e.g. TB diagnostics.
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3. Single Nucleotide Polymorphisms
SNPs are single-base differences in DNA between
individuals in a population Most frequent type
of genetic variation Attractive biomarkers for
drug discovery development Challenge is to
identify SNPs that influence or change
pharmacokinetics, pharmacodynamics and/or
clinical end points
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4. Tissue Engineering
Most promising for skeletal tissues that have the
capacity to regenerate. Products produced in the
laboratory from human animal tissue are being
developed to bring about tendon and cartilage
repair. Bone morphogenic proteins have been
successfully used in periodontal bone
regeneration.
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5. Vital Organs

Difficult to achieve and costly LIFE initiative
established with 60 international participants
pooling their expertise and capabilities
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6. Novel Antibacterial Agents
Current trend A target based approach based on
bacterial genomes e.g. a peptide that inhibits
the enzyme deformylase New drugs based on
host/pathogen interactions e.g. the drug Xigris
for the treatment of sepsis
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7. Monoclonal Antibodies
The prediction is that more than half of new
active substances developed in the next 10-15
years will be the result of antibody
research. Reason shorter development time for
MAbs. MAbs have been developed for a range of
diseases including cancers, organ rejection
rheumatoid arthritis.
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8. HIV/AIDS
New approaches to complement highly active
retroviral treatment (HAART) Entry inhibitors
e.g. T-20 which aligns itself with part of viral
gp41 and prevents the virus from fusing with the
host cell. Immune based therapies designed to
optimise the host immune response to keep the
virus at bay.
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DIAGNOSTICS
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Biological Assays
Biological assays are needed to support
biotechnology derived products. Biological assay
measures biological activity based on a specific
functional, biological response of a test
system. Examples In vitro tissue based. In vitro
cell line based. Reporter gene based. Biosensors
that detect binding of cells to immobilised
ligands. Kinase receptor assay that allows for
more rapid assessment of immunogens.
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VACCINES
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Challenges for Vaccine Development
Challenges for vaccine development is the same
for many infectious diseases Vaccines need to
be Safe Effective Broad-spectrum Simple,
transportable vectors Easily administered Provide
long-term immune memory Provide protection at the
site of infection
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AIDS Vaccines
Several vaccines have been developed 70 phase I
trials 5 phase II trials 2 phase III trials
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Current AIDS Vaccine Research
Enhancing the immunogenicity of specific HIV
peptides. Enhancing antibody responses to
regions of HIV proteins protected from immune
detection. Developing new vectors and more
efficient methods for producing
vectors. Developing more efficient methods to
determine T-cell receptor specificities
cytokine profiles.
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Identification of host genes that confer
resistance to infection to determine which
vaccines are best suited to which
populations. Understanding the response of the
human immune system to candidate vaccines.
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Malaria Vaccine Research
Receives roughly 10-fold less funding than HIV
vaccine development. Cost of developing a
malaria vaccine is estimated at 500 m. Several
international initiatives to support the
development of a malaria vaccine e.g. European
Malaria Initiative, Gates Foundation, US NIH
Department of Defense.
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Several malaria vaccines are in or close to
clinical trials. The main obstacle is the
capacity for producing clinical grade material
for protein-based vaccines for performing field
trials for all types of malaria vaccines. At
lease 5 000 candidate proteins have been
identified. There is a lack of validated models
that reliably predict the degree of protection in
humans.
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GENE THERAPY
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The retina is potentially the best candidate for
gene therapy. Gene therapy has been successfully
used to reverse blindness in 3 dogs with a rare
inherited disease. The amount of vector virus
injected into the eye is 0.001 of that used for
systemic diseases. Blood-ocular barrier
separates the eye from the rest of the body and
the virus is less likely to have a systemic
effect.
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DELIVERY SYSTEMS
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Protein Transduction Technology
Developing field with potential applications
in Gene therapy where it is preferable to
deliver the gene product. Vaccine delivery e.g.
the VP22 technology being used to develop
hepatitis HPV derivatives. Drug delivery e.g.
synthetic peptide derivatives or peptoids can be
covalently linked to small drugs for delivery
uptake at different sites in the body. Peptoids
are more cost effective, easier to synthesise,
more resistant to proteases than synthetic or
naturally occurring peptides.
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Reproductive Medicine Highly Controversial
Diagnostics Pre-implantation genetic diagnosis
(PGD) used to screen early embryos for heritable
genetic defects or age-related genetic
abnormalities
Therapeutics Stem cell engineering for
therapeutic and regenerative medicine Embryonic
stem cells (5-6 days old) may be used to
reconstitute defective organ systems
Reproduction Reproductive cloning Twin cloning
via embryo splitting
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Academia Industry

• Much of therapeutic innovation in recent
  decades resulted from biotechnology and
  pharmaceutical industry sponsored efforts.

• Increasing pressures, competition, less funding
  in public sectors has led to new challenges in
  industry-sponsored clinical research.

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Predicted Genomic Impact by Therapeutic Area
Investors no longer as eager to invest in
proteonomics Viewed as low profit commodity Eager
to see tangible therapeutic diagnostic products
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6. Artificial Cells
Artificial cells will make it possible to combine
nanoscale efficiency, self-organisation
adaptability for therapeutic diagnostic
applications. Many individual components have
been developed The main challenge is to
encapsulate components in a single compartment
to have sequential and controlled activities.