賽亞 賽亞 vitagenomics pharmacogenomics: a trend in post genome era for personalized medicine...
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賽亞賽亞 VitaGenomics
Pharmacogenomics: A Trend in Post Genome Era for Personalized Medicine
Chih-Ping Yang, Ph.D.
October 25, 2002
賽亞賽亞 VitaGenomics
Our Fate:
Nature
vs.
Nurture
1. Defective gene causes disease.
2. Defective genes + environmental factors
cause disease.
賽亞賽亞 VitaGenomics
MEDICAL CARE (20TH CENTURY)
DISEASEDOMINANT
PATHOLOGY
DIAGNOSIS THERAPY
賽亞賽亞 VitaGenomics
MEDICAL CARE (21st CENTURY)
PREDISPOSING FACTORS DISEASE
Public Health Education
PREVENTION
Therapy
DOMINANT PATHOLOGY
Diagnosis
賽亞賽亞 VitaGenomics
HEART FAILURE
Hypercholesterolemia
Coronary artery
narrowing
RISK IDENTIFIED
AnticoagulantsStatins/FibratesBypass surgery
Angioplasty
Myocardial infarct
Statins Fibrates
Heart failure
賽亞賽亞 VitaGenomics
BREAST CANCER
BRCA 1, BRCA 2, etc.Breast Cancer
RISK IDENTIFIED
Metastasis
CounselingTamoxifen
Her-2 monoclonal
SurgeryChemotherapy/
Radiation
賽亞賽亞 VitaGenomics
Human Genome Project
• 1985 US DOE initiated the concept• 1990 US Congress approved the $3 billion,
15-year program led by NIH• 1998 New sequencing technology available,
the commercial industry joined the race.• 2000 “rough draft” sequence completed.
During the 90’s, numerous biotech companies were started to capitalize the enormous opportunities.
賽亞賽亞 VitaGenomics
HGP data reported by Celera and Public Consortium
“The Sequence of the Human Genome” “Initial Sequencing and Analysis of the Human Genome”
48 pages62 pages
2/16, 2001
2/15, 2001
賽亞賽亞 VitaGenomics
Pharmacogenomics
The use of genomics approaches to elucidate drug response:
• Via DNA: genetic approach (pharmacogenetics).
• Via RNA: expression profiling.
• Via Protein: Proteomics.
賽亞賽亞 VitaGenomics
賽亞賽亞 VitaGenomics
SNP (Single Nucleotide Polymorphism)
Every individual has ~0.1% of the genome that is different. In average, every 1Kb has a SNP can be used as a marker on the genome.
賽亞賽亞 VitaGenomics
Applications of the SNP AnalysisApplications of the SNP Analysis
• Disease gene hunting
• Prognostics / diagnostics of genetic risks
• Pharmacogenomics and drug discovery
• Personalized medicine
賽亞賽亞 VitaGenomics
Population A Population B
Most likelyDrug acts on therapy
Most likelyDrug has no efficacy
Drug treatment Choose other drug
SNP and Drug Response Evaluation
賽亞賽亞 VitaGenomics
Genetic basis for individual differences in drug absorption and metabolism
For example:A drug is safe for 70% of people,ineffective for 25%,harmful for 5%
Genetic Variation
Polymorphisms vary
across populations
賽亞賽亞 VitaGenomicsGENE X GENE Y
%
%
Normal Population
Patient Population
SNP & Disease Gene ID
賽亞賽亞 VitaGenomics
Number of SNP Candidates
Number of DNA Samples
SNP Discovery
Resequencing and in silico analysis to find putative SNPs
SNP Validation
Confirmation of true SNPs and allele frequency estimation
SNP Screening
Applying SNPs in research studies
Technology: BigDye™ Terminator Cylce Sequencing Kits
Technology: SNaPshot™ Multiplex System
Technology: TaqMan® 5’Nuclease Assay and MGB Probes
SNP Validation Process
賽亞賽亞 VitaGenomics
Target ID Drug screen
High throughputscreen
Lead compound
Clinical trial
Diagnosis/Therapy
Chemical
Natural
Combinatorial
Proteomics
Genomics
SNP applications> 7 years
SNP applications2-4 years
SNP and Drug Development
賽亞賽亞 VitaGenomics
Advantages to the pharmaceutical industry:
• Increase efficiency of target and lead discovery• Reduce timelines and costs of clinical trials• Product differentiation in the market place
Trends in Biotechnology 19, 491-496 (2001).
Personalized medicine
賽亞賽亞 VitaGenomics
Advantages to patients and clinicians:
• Higher probability of desired outcome with a drug
• Low probability of side effects
• Preventive strategies
• Focused therapies
• Reduce costs
• Better health and better healthcare
Trends in Biotechnology 19, 491-496 (2001).
Personalized medicine
賽亞賽亞 VitaGenomics
SNP or DNA/Protein marker discovery• Access to patient populations• Genotyping costs & Technology development• Computational methodologiesMarker utilization in practice• Assay platform development• Large scale data & knowledge management• Ethical, legal, & social considerations• Physicians & patients education Trends in Biotechnology 19, 491-496 (2001).
Challenges to Personalized Medicine
賽亞基因科技 Vita Genomics, Inc.
賽亞賽亞 VitaGenomics
賽亞基因科技 Vita Genomics, Inc.
Overview
Established in March, 2001 Capital of NT$ 3.5 billion Collaborate with Celera Genomics Operates at the Taipei , Tainan and USA Projected personnel to reach 300 in 3 years
賽亞賽亞 VitaGenomics
Mission
Become a premier genomics-based biotechnological and biopharmaceutical company in the Asia Pacific region
賽亞賽亞 VitaGenomics
Vita Genomics Technology Platform
SNP Analysis
STR-based Genotyping
Bioinformatics Microarray
Clinical Sample Collection
High-Throughput DNA Sequencing
Vita Genomics Has Established:
A Seamlessly Integrated Technology Platform for Pharmacogenomics & other Genomics Research
賽亞賽亞 VitaGenomics
Phenotypes
Patient databases
Phenome
Genotypes
Genomics databases
Genome
Vita Genomics
Integration of Biological Data
DNA Sequencing
SNP & STR Genotyping
Microarray Study
賽亞賽亞 VitaGenomics
Diseases & Projects of Interest • Infectious Diseases prevalent in Asia (e.g.,
Hepatitis B & C)
• Cancers commonly found in the Chinese population (e.g., hepatoma, breast cancer, nasopharyngeal carcinoma, oral cancer, etc.)
• Chronic diseases such as diabetes, asthma, depression, etc.
• Pharmacogenomics studies (The use of genomics approaches to elucidate drug response)
賽亞賽亞 VitaGenomics
April 22, 2002
Over 3 Million Americans Are
Infected With the Stealth Virus.
Most Don’t Know It.
Treatment With Interferon Only Cures 40-50%
Patients
賽亞賽亞 VitaGenomics
人類基因組型與人類基因組型與慢性 C 型肝炎治療反應之關聯性
全球 200 million 人感染急性 C 型肝炎
20% 自行痊癒 80% 慢性 C 型肝炎
80% 有症狀
Ribavirin + 干擾素
2-5% 患者接受治療
50% 無效 50% 有效
20% 無症狀