February 3, 2016 1 February 3, 2016 Prof. Dan Peer, Director , Laboratory of NanoMedicine, Dept. of Cell Research & Immunology and Dept. of Materials science & Engineering, Tel Aviv University, Israel Omics-Based Nanomedicine: the Future of Personalized Medicine
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Omics-Based Nanomedicine: the Future of Personalized Medicine
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February 3, 2016 1
February 3, 2016
Prof. Dan Peer,
Director , Laboratory of NanoMedicine,
Dept. of Cell Research & Immunology
and Dept. of Materials science & Engineering,
Tel Aviv University, Israel
Omics-Based Nanomedicine: the Future of Personalized Medicine
February 3, 2016 2
Think different - Innovation
•Creativity
•Motivation
•Persistent
February 3, 2016 3
How do we solve problems ?
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Breaking the Cycle
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Until today – “Blockbuster drugs” – everyone gets the same drug
Efficacy ?
~ 15-20% of patients at most – will benefit
New area – Make it Personal
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The ability to sequence the Genome (DNA),
Transcriptom (RNA) and to edit Genes
February 3, 2016 13
Precision Medicine
Price in 1994: ~ $1B / One human Genome
Price in 2014: ~ $2000 / One human Genome
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Each person react differently to drugs
1. Genome (genes) 2. Environment
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What can we do with all the information from sequencing ?
Sequence patients with a particular
disease (e.g. Cancer)
Learn about the mutations and
genes that are overexpressed
Design and synthesis new drugs
based on RNA that fits the patient
profile
Design and synthesis of new
delivery systems
February 3, 2016 16
• Can make any target “druggable”
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“Playing” GOD with genes– silence genes, up
regulating gene expression and editing
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RNA / DNA technologies is ready to go BUT the DELIVERY
of these molecules into specific cells types is not.
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Targeted(Delivery(to(Tumors(
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:components 3We need to have
The drug: RNA sequence
The delivery system that can package the drug
The targeting moiety : provide an address to the
delivery system (work like GPS) and bring it into the
diseased cell
The drug
The
delivery
system
Targeting
(GPS
system)
February 3, 2016 23
Laboratory of NanoMedicine
Delivery systems and protein
engineering
Exome / transcriptome analysis
and Target Discovery & Validation
February 3, 2016 24
Landscape of cancer genomics analyses
Tailored medicine
February 3, 2016 25
Collaboration with Dept. of
Neurosurgery, Sheba
Hospital
Dr. Zvi R. Cohen
Localized RNAi Therapeutics of Chemoresistant
Grade IV Glioma Using Hyaluronan-Grafted Lipid-
Based Nanoparticles
February 3, 2016 26
Looking for Glioma unique surface markers that can be used as GPS-like system
Cohen et al. ACS Nano 2015
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Laminar fluid flow
Controlled, time invariant mixing
Rapid mixing (3 ms-1): Timemix < Timeppt
Reaction volumes ~ 14 nL
Low energy input
Total flow rates from 4 mL/ min to 20 mL/min
Parallelized mixers enable seamless scale-up
Microfluidics Enables Exquisite Control Over Manufacturing Process – CMC of Nanoparticles packaging RNA molecules
EtOH + Lipids pH4 Buffer + RNA
Rapid & Controlled Mixing
(Chaotic Advection)
Mixer design by:
Stroock et al., Science
2002
Channel
Dimensions:
~100 µm
Staggered
Herringbone
Mixers (SHM)
RNA-Lipid
Nanoparticles
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Choosing the appropriate therapeutic target (the drug):
PLK1- cell cycle regulator
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Orthotopic GBM mouse model
Cohen et al. ACS Nano 2015
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Therapeutic gene silencing prolongs the survival of GBM-bearing mice.
Cohen et al. ACS Nano 2015
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How do we progress into the clinic ?
Sequence glioma patients (DNA and
RNA)
Learn about the mutations and
genes that are overexpressed
Design and synthesis new drugs
based on RNA that fits the patient
profile
Scale up the production of
Nanoparticles with RNAs
February 3, 2016 32
Targeting Mantle Cell Lymphoma with Nanomedicines
•Aggressive form of B-cell malignancy.
•Low Incidence: 1-2/100,000 per year (6%-9% out of
total malignant lymphomas).
•Rate of men to women - 3 : 1
•Median age: 60
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• A chromosomal translocation - t(11;14)(q13;q32)
Strong
Promotor
Cyclin D1 overexpression
Chromosome 11
Chromosome 14
Chromosomal translocation
IGH
Cyclin D1
Genetic characterization of Mantle Cell Lymphoma (MCL)