cost-effectiveness economically feasible basic biology...
TRANSCRIPT
![Page 1: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/1.jpg)
Introduction
What is Biotechnology? - Purposeful design and modification/assembly of bio-oriented materials (e.g.,
proteins/enzymes, microorganisms, plant/animal cells, tissues, stem cells etc..)
and unit processes to benefit humans or make a profit.
- Use and applications of biological system (cells, tissues etc..) or biomolecules (enzymes/proteins, antibodies, DNA/RNA) and key technologies to produce
valuable products at commercial scale and to treat diseases:
Cost-effectiveness economically feasible
Basic Biology / Medical sciences - To discover and understand the underlying mechanisms of behaviors
and disorders in living organisms
![Page 2: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/2.jpg)
Traditional Biotechnology (Before 1970) - Broad definition of Biotech : Using a biological system to make products
- Food processing : Fermented foods, Brewery, Dairy products, etc.
Biological process of brewing beer : conversion of starch to sugar followed
by addition of specific yeast
- Agriculture : Modifications of living plants for improved yield of food crops via
artificial selection and hybridization: Breeding
ex) Crops with reduced vulnerability to frost, draught, and the cold
Simple process
- Direct use of or isolation from original biological sources
- Fermentation: production of acetone using Clostridium acetobutylicum
Definition of Biotechnology based on the use of techniques/methods
![Page 3: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/3.jpg)
• Use of recombinant DNA technology since 1973
- Cohen and Boyer : gene manipulation techniques to cut and paste DNA
(using restriction enzymes and ligases) and transfer the new DNA into bacteria.
Revolutionize traditional biotechnology
• Combined use of different disciplines:
- Biology-based knowledge : Cell biology, genetics, molecular biology, etc
- Knowledge linked with practical applications :Biochemical Eng, Bioinformatics,
computational design, Organic chemistry etc.
• Use of genetically engineered microorganisms
- Enabling the production of existing medicines or products easily and cheaply
(ex: Insulin (51 amino acids) : discovered by Banting and Macleod from Univ. of Toronto, awarded Nobel Prize in 1923. Assistants : Charles Best (not awarded)
- First genetically engineered synthetic insulin (Humulin) by E. coli in 1982)
• Traditional Biotechnology industries : adopts new approaches and modern techniques
to improve the quality and productivity of high value-added products
Modern Biotechnology (After 1970s)
![Page 4: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/4.jpg)
Impact of recombinant DNA technology on the production of proteins
• Overcomes the problem of source availability : allows the manufacture of any protein in whatever quantity it is required
• Overcomes the problem of product safety:
Transmission of blood-born pathogens such as hepatitis B, C, and HIV
via infected blood products
• Provides an alternative to direct extraction from inappropriate or dangerous source materials : The fertility hormones( FSH and hCG) from the urine of pregnant women; Urokinase from urines
• Facilitates the generation of newly designed proteins:
Therapeutic proteins or enzymes with desired property
![Page 5: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/5.jpg)
• Development of therapeutics based on underlying mechanisms of diseases
- Development of new methods to cure diseases : Gene and cell (stem cells) therapies, therapeutic proteins
• Production of valuable products at commercial scale
Organic acids, Antibiotics, Amino acids, Proteins(enzymes), Biofuels, Vitamins,
Hormones, Alcohols, Fermented foods, Fine chemicals, etc..
• Development of tools and methodology Expression systems, Gene synthesis/Sequencing, Genome editing, Diagnosis,
Delivery, Purification process, Formulation, Bioassays
Major focus of Biotechnology
![Page 6: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/6.jpg)
Integration of biological sciences with Engineering principles
cost-effectiveness
Required disciplines
- Biology
- Physical, organic chemistry / Pharmacology, Electronics
- Biochemical engineering : Extension of chemical engineering principles to biological system Mass/Heat/Energy transfer, - Thermodynamics Bioreaction engineering, plant design, process control / optimization, and separations
Basic Biology
Biotechnology Bio-industry - Pharmaceutical - Biotech. company Engineering principles
Biotechnology is a multi-disciplinary field
![Page 7: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/7.jpg)
Recombinant E. coli
G protein-coupled receptor(GPCR)
DNA microarray
Gene therapy using adenovirus Nanobiotechnology
![Page 8: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/8.jpg)
• Health care / Diagnostics : - Development of therapeutics: efficacy, toxicity - Diagnosis : early detection and prevention of diseases
• Agriculture : Crop production with high yield and quality • Bio-based process: Pollution, CO2 emission, global warming • Alternative energy (Bio-energy) : - Depletion of fossil fuels - Use of renewable sources :Corn, sugar cane, cellulose - Cost (?)
Major application areas
![Page 9: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/9.jpg)
• Protein engineering : Design of proteins/enzymes based on structural and mechanistic knowledge, molecular evolution, computational design
• Metabolic pathway engineering: Design of more efficient metabolic pathways:
high yield of target product, low by-product
• Computational modeling and optimization: Systems Biology, Genome- and
proteom-wide analyses
• Nano-biotechnology : Integration of nanotechnology
- Use of NPs for diagnosis, drug delivery, and imaging
- Nano-medicine
Key fields
![Page 10: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/10.jpg)
• Cell culture engineering : Cultivation of microorganisms and mammalian cells
- Hybridoma technology : A technology of forming hybrid cell lines (called hybridoma) by fusing a specific antibody-producing B cell with a myeloma
(B cell cancer) cell that is selected for its ability to grow in culture media.
• Tissue engineering : Use of a combination of cells, engineering and materials/ methods, and suitable biochemical and physio-chemical factors to repair or replace portions of or whole tissues (i.e., bone, cartilage, blood vessels, bladder, skin, muscle etc,--> artificial organs )
• Synthetic biology : Designing and constructing biological devices and bio
logical systems for useful purposes.
- Creation of new bio-systems (Cells and biomolecules): Systematic, hierarchical
design of artificial, bio-inspired system using robust, standardized and well-
characterized building blocks or parts
• Separation technology : Recovery and purification of a target product
![Page 11: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/11.jpg)
Branches of Biotechnology
• Blue biotechnology : Marine and aquatic applications of biotechnology
• Green biotechnology : Agricultural applications
Plant biotechnology
• Red biotechnology : Medical applications
Nanomedicine, Regenerative medicine
• White biotechnology : Industrial applications
- Production of bio-chemicals using bioprocess
![Page 12: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/12.jpg)
New paradigms in Biotechnology
• Massive and high-speed analysis system
- Genome and proteom-wide approach : Systemic approach
- Huge amounts of relevant knowledge,
• Genomics (Gene chips) : Sequences of more than few hundreds genomes
- 1 million genes / chip
- Gene (mRNA) expression profiling in high throughput way
- Single nucleotide polymorphism (SNP)
• Proteomics (2-D gel, LC/MS, protein microarray)
- Functional genomics
- Bio-molecular interactions (Interactoms)
• Development and commercialization of target products
- Bioinformatics
Genome- and proteom-wide analyses: Global analysis Integration of high-throughput analysis system
![Page 13: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/13.jpg)
Bio-based economy: Impact on global economy
Shift from petroleum-based economy - Exhaustion and soaring price of petroleum (> $ 100 /gallon)
- Environmental issue
Global warming (greenhouse gas, CO2 , emission)
Pollution
• Development of renewable source-based Bioprocess
• Replacement of chemical processes with Bio-based ones
White Biotechnology
![Page 14: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/14.jpg)
Company Products
BASF
Vitamin B-2 Methoxy isopropyl amine (chiral intermediate) Styrene oxide Amino acids
Eastman Chemical / Genencor Ascorbic acid
Degussa
Acrylamide Fatty acid – derived esters Polyglycerine ester Organo modified silicones and oleochemicals
Celanese / Diversa
Acetic acid Polyunsaturated fatty acids Non-digestible starch Polylactic acid (PLA)
Cargill Polylactic acid (PLA) (140,000 MT/yr)
DuPont / Genencor 1,3-Propanediol Terephthalic acid Adipic acid
Chevron / Maxygen Methanol
Typical examples of Bio-Products
![Page 15: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/15.jpg)
Cell culture
Bioconversion
Feedstock Bioprocessing Product
GAS
LIQUID
SOLID
PRODUCT
LINES
Biocatalyst
Cells Bioreactor
Recovery
product
Feedstock Bioprocessing
Gas − Syn. Gas − CO2
− Organic vapor
Liquid − Organic − Sugar solution
Solid − Biomass − Consumer Waste
Bioconversion
by enzymes − Ambient to Extreme
Cell culture − Bacteria/yeast −Mammalian cells − Ambient to Extreme
Bioreactors − Continuous Systems − Membrane − Batch or Fed-batch
Media - Aqueous - Organic solvent
Separation /purification − In situ − Secondary
Pharmaceuticals Fine chemicals Specialty Chemicals Feedstock Bulk chemicals
General scheme for bioprocess
Products
![Page 16: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/16.jpg)
Value chains from renewable sources
![Page 17: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/17.jpg)
Alternative energy sources
Production of biofuels from renewable sources
• Increase in the yield and alcohol tolerance - Redesign of pathway for the ethanol production in yeast to use raw materials :
corn starch, cellulose, soybean, sugar cane
- Elucidation of enzyme mechanisms
- Redesign of pathway to increase the yield and to reduce by-products
- Design of critical enzymes in the pathway
• Process development : Fermentation process
• Separation and concentration
Role of Agricultural Biotech in the production of biofuels ? Adverse effects due to the production of biofuels from corn ?
![Page 18: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/18.jpg)
Enzymes play a key role in Bio-based economy
Energy and Environmental issues - Depletion of fossil fuels - Limitation to CO2 emission (Kyoto protocol)
Renewable source-based economy
Bio-based process
Enzymes
Petrochemical-based economy
Chemical process
Use of enzymes for biofuel and biochemicals from renewable biomass such as starch and cellulose amylase, cellulase etc.
![Page 19: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/19.jpg)
Biomolecular Eng. Lab.
Enzymes : Biocatalysts
- Cleaning (Detergents) - Textiles - Starch Processing - Leather - Baking - Pulp and Paper - Food and Specialties - Cosmetics
Most proficient catalysts with high specificity Competitive and cost-effective processes
Chiral drugs
Chiral intermediates
Semisynthetic antibiotics
Organic acids
Synthesis of specialty chemicals
Use for biosciences
DNA polymerase: Thermostability, fidelity
Restriction enzymes: Specificity
Alkaline phosphatase, Peroxidase
Use for daily life
![Page 20: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/20.jpg)
Chemical company devoting to Biotechnology : BASF
Ecoflex®
Emphasis on Bio-products mainly using enzymes
![Page 21: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/21.jpg)
Therapeutic proteins
Small molecule-based drugs : Efficacy, side effect, safety
Therapeutic proteins : High efficacy and safety, less toxicity
- Antibodies, proteins, enzymes, peptides etc.
ex) EPO, Interferon, Insulin, Avastin, Enbrel, Remicade, Herceptin,
EPO (Erythropoietin) : Stimulating the proliferation of red blood cells
Herceptin : Mab against EGFR2(Epidermal growth factor receptor 2) Avastin : Mab against VEGF (Vascular endothelial growth factor) Remicade: Mab against TNF-α (Tumor necrosis factor- α)
World market
- EPO alone : ~ $ 11 billion per year
- Remicade : ~ $ 9 billion per year
- $ 50 Billion (2007) $ 190 Billion (2015)
- Intensive investment in monoclonal antibodies: Biosimilar
Therapeutic proteins will form the back-born of future biotech market
![Page 22: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/22.jpg)
Brand name Active ingredient
Type Class Treatment Company 2013 global sales (US$ billion)
Patent expiry EU/US
Humira adalimumab Antibody TNF inhibitor Arthritis Abbott/Eisai 10.7 Apr 2018/ Dec 2016
Remicade infliximab Antibody TNF inhibitor Arthritis Merck/Mitsubishi 8.9 Aug 2014/ Sep 2018
Rituxan rituximab Antibody Anti-CD20 Arthritis, NHL Roche/Biogen 8.6 Nov 2013/ Dec 2018
Enbrel etanercept Antibody TNF inhibitor Arthritis Amgen/Pfizer 8.3 Feb 2015/ Nov 2028
Lantus insulin glargine Protein Insulin receptor Diabetes Sanofi 7.8 2014/2014
Avastin bevacizumab Antibody Anti-angiogenesis Cancer Roche 7.0 Jan 2022/ Jul 2019
Herceptin trastuzumab Antibody Anti-HER2 Breast cancer Roche 6.8 Jul 2014/ Jun 2019
Neulasta pegfilgrastim Protein G-CSF Neutropenia Amgen 4.4 Aug 2017/ Oct 2015
Top 8 blockbuster biologicals (2013)
![Page 23: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/23.jpg)
1 2
3 3
2
1 CDRS
FR
VL VH
Structural and functional features of antibodies
![Page 24: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/24.jpg)
• Complicated process for selecting cell lines and
the production using mammalian cells very expensive
• Intellectual property barriers
• Tend to aggregate due to large size (~ 150 KDa)
• Difficult to penetrate inside the cells
• Limited binding affinity due to confined binding surface
Non-antibody scaffold to replace antibodies
High-level soluble expression in bacteria
High stability (thermodynamic, pH)
Easy design of binders with high affinity for a target
Low immunogenicity and cytotoxicity
Drawbacks of immunoglobulin antibodies
![Page 25: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/25.jpg)
Therapeutics based on non-antibody scaffold
Development of new therapeutics with high efficacy and low side effects
from non-antibody protein scaffolds
Designer therapeutic proteins : Specificity and binding affinity
IP issue and cost-effectiveness
GlaxoSmithKline, Amgen Bristol-Myers-Squibb, Boehringer Ingelheim Eli Lilly, Roche, Avidia, Ammunex. Affibody, Ablynex,
Adnexus Therapeutics …….
Strategic alliance or merger between big pharma and biotech companies
New paradigm in therapeutic proteins
- Technology and idea - Financial investment
![Page 26: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/26.jpg)
Non-antibody scaffolds
Human fibronectin Human lipocalin
Z domain of Staphylococcal protein A
Ankyrin Repebody
![Page 27: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/27.jpg)
Disease Product name
Developer
Sales (US$Millions) Features 2004 2007
Gaucher’s
Ceredase® Genzyme 443 N/A Glucocerebrosidase (β-Glucosidase)
Purified from human placenta
Cerezyme® Genzyme 932
(2005) 1,048
Produced in CHO cells
3 Exoglycosidases process for Terminal Mannose
Fabry’s Fabrazyme® Genzyme 209 397 α-galactosidase
Mannose-6-phosphate for Glycotargeting Replagal TKT 57 168
MPS-1 Aldurazyme® Genzyme 12 204 α –L-iduronidase
Pompe Myozyme® Genzyme Approved
(2006) α-glucosidase
Therapeutic Enzymes : Enzyme replacement treatment
Treatment of Gaucher’s disease by Cerezyme costs up to $550,000 annually: Orphan drug and life-long treatment
Most of therapeutic enzymes : glycoproteins
![Page 28: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/28.jpg)
Glucocerebrosidase (β-Glucosidase)
- Found by Phillipe Gaucher in 1882
- Biochemical basis for the disease in 1965 by Brady et al..
Glucosyl
CH2-CH-CH-CH=CH-(CH2)12-CH3
O=C-CH2-CH2-CH2-(CH2)n-CH3 N OH
Ceramide
OH-CH2-CH-CH-CH=CH-(CH2)12-CH3
O=C-CH2-CH2-CH2-(CH2)n-CH3 N OH
Glucose Ceramide
Gaucher’s Disease : Lysosomal Storage Disease
Autosomal recessive inheritance
- Caused by a recessive mutation in a gene located on chromosome 1, affecting both males and females
- Most common of the LSD
Glucocerebroside: Constituent of red and white blood cell membranes
![Page 29: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/29.jpg)
Lysosomal storage diseases (LSDs): Lysosomal Enzymes
Lysosomes: Cellular organelles containing acid
hydrolase enzymes to break down waste materials and cellular debris
Cells’ garbage disposal system • Digestive organelle in the cell • Contains ~40 hydrolytic enzyme • Acidic pH (about pH4.8) within the
lysosome : the activity of lysosomal enzymes
(1) The ER and Golgi apparatus make a lysosome
(2) The lysosome fuses with a digestive vacuole
(3) Activated acid hydrolases digest the contents
(LSD) Lysosome
Nucleus
Mitochondria
Lysosome with substrate accumulation
(Normal cell) (LSD cell)
![Page 30: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/30.jpg)
Normal cells Glucocerebrosides
Glucocerebrosides
Digestive vacuole
Gaucher cells
Digestive vacuole
Glucocerebrosidase
Incomplete digestion
Exocytosis
Residual vacuole
glucose ceramide +
Residual vacuole accumulated
No exocytosis
1/ 40,000~60,000 (Jew 1/~500) Swollen vacuoles Gaucher cells Accumulation in spleen, liver, kidney, brain Enlarged spleen and liver, liver malfunction, neurological complications etc..
Gaucher’s disease : Occurrence and symptoms
Distended abdomen
![Page 31: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/31.jpg)
Diagnostics
• Diagnosis of disease as early as possible :
Best solution compared to treatments
• Prediction and treatment of diseases based on individual
genome sequence
- Personalized medicine
- Treatment with appropriate therapeutic agents
• Analysis / Detection of disease biomarkers:
- Invasive or non-invasive analysis
- Isolation and analysis of circulating tumor cells and DNAs
• Integration with nanotechnology : Sensitivity and accuracy
![Page 32: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/32.jpg)
Regenerative medicine
Translational research for replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function
![Page 33: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/33.jpg)
Genome editing • A type of gene engineering in which DNA is inserted, replaced, or removed from a
genome using artificially engineered nucleases, or "molecular scissors."
• Four families of engineered nucleases
- Meganucleases: Endodeoxyribonucleases with a large recognition site
(double-stranded DNA sequences of 12 to 40 base pairs)
- Zinc finger nucleases (ZFNs)
- Transcription Activator-Like Effector Nucleases (TALENs)
- CRISPR (Clustered regularly interspaced short palindromic repeats)/Cas system
![Page 34: Cost-effectiveness economically feasible Basic Biology ...bel.kaist.ac.kr/extfiles/lecture/2015spring/bs223/Introduction.pdf · What is Biotechnology? ... efficacy, toxicity - Diagnosis](https://reader034.vdocuments.net/reader034/viewer/2022051722/5a9f887d7f8b9a0d158cfb0d/html5/thumbnails/34.jpg)
Biotechnology will have the greatest impact on humans
in the future in terms of health care, life-style, and economy.
- Therapeutic proteins
- Bio-based economy : High-value compounds by bioprocess
- Diagnostics
Modern Biotechnology constitutes a variety of diverse areas
and technologies, requiring interdisciplinary collaborations.
Perspectives