Archive for the ‘Warren Alpert Foundation Prize Recipients’ Category

Lectures by The 2017 Award Recipients of Warren Alpert Foundation Prize in Cancer Immunology, October 5, 2017, HMS, 77 Louis Paster, Boston

Reporter: Aviva Lev-Ari, PhD, RN

Top, from left: James Allison and Lieping Chen. Bottom, from left: Gordon Freeman, Tasuku Honjo (NOT ATTENDED), Arlene Sharpe.

Aviva Lev-Ari, PhD, RN was in attendance and covered this event LIVE


The 2017 Warren Alpert Foundation Prize has been awarded to five scientists for transformative discoveries in the field of cancer immunology.

Collectively, their work has elucidated foundational mechanisms in cancer’s ability to evade immune recognition and, in doing so, has profoundly altered the understanding of disease development and treatment. Their discoveries have led to the development of effective immune therapies for several types of cancer.

The 2017 award recipients are:

  • James Allison, professor of immunology and chair of the Department of Immunology, The University of Texas MD Anderson Cancer Center – Immune checkpoint blockage in Cancer Therapy strictly Genomics based drug
  1. 2017 FDA approved a genomics based drug
  2. and co-stimulatory signals
  3. CTLA-4 blockade, CD28, AntiCTLA-4 induces regression of Transplantable Murine tumor
  4. enhance tumor-specific immune response
  5. Fully antibody human immune response in 10,000 patients – FDA approved 2011
  6. Metastatic melanoma – 3 years survival, programmed tumor death, PD-1, MHC-A1
  7. Ipi/Nivo vs. Ipi – combination – 60% survival vs Ipi alone
  8. Anti CTA4 vs Anti-PD-1
  9. responsive T cell population – MC38 TILs
  10. MC38 Infiltrating T cell populations: T-reg, CD4, Effector, CD8, NKT/gamma-delta
  11. Checkpoint blockage modulates infiltrating T cell population frequencies
  12. T reg correlated with Tumor growth
  13. Combination therapy lead to CURE survival at 80% rate vs CTAL-4 40% positive outcome

Not Attended — Tasuku Honjo, professor of immunology and genomic medicine, Kyoto University – Immune regulation of Cancer Therapy by PD-1 Blockade


  • Lieping Chen, United Technologies Corporation Professor in Cancer Research and Professor of immunobiology, of dermatology and of medicine, Yale University – Adoptive Resistance: Molecular Pathway t Cancer Therapy – focus on solid tumors
  1. Enhancement – Enhance normal immune system – Co-stimulation/Co-inhibition Treg, and Cytokines, adoptive cell therapy, Lymphoid organs stores
  2. Normalization – to correct defective immune system – normalizing tumor immunity, diverse tumor escape mechanisms
  3. Anti-PD therapy: regression of large solid tumors: normalizing tumor immunity targeting tumor microenvironment: Heterogeneity, functional modulation, cellular and molecular components – classification by LACK of inflamation, adaptive resistance, other inhibitory pathways, intrinsic induction
  4. avoid autoimmune toxicity,
  5. Resetting immune response (melanoma)
  6. Understad Resistance: Target missing resistance or Adaptive resistance Type II= acquired immunity
  • Gordon Freeman, professor of medicine, Dana-Farber Cancer Institute, Harvard Medical School – PD-L1/PD-1 Cancer Immunotherapy
  1. B7 antibody
  2. block pathway – checkpoint blockage, Expand the T cells after recognition of the disease. T cell receptor signal, activation, co -stimulatory: B71 molecule, B72 – survival signals and cytokine production,.Increased T cell proliferation,
  3. PDL-1 is a ligand of PD 1. How T cell die? genes – PD1 Gene was highly expressed,
  4. Interferon gamma upregulate PD-L1 expression
  5. Feedback loop Tumor – stimulating immune response, interferon turn off PD1
  6. PD-L1 and PD-L2 Expression: Interferom
  7. Trancefuctor MHC, B7-2
  8. PD-L! sisgnat inhibit T-cell activation: turn off Proliferation and cytokine production — Decreasing the immune response
  9. T cell DNA Content: No S-phase devided cell
  10. PD-L1 engagement of PD-1 results in activation : Pd-1 Pathway inhibits T Cell Actiivation – lyposite motility,
  11. Pd-L2 is a second ligand for PD-1 and inhibits T cell activation
  12. PDl-1 expression: BR CA, Ovarian, Colonol-rectal, tymus, endothelial
  13. Blockage of the Pathway – Immune response enhanced
  14. Dendritic cells express PD-L1, PD-L2 and combination of Two, Combination was best of all by increase of cytokine production, increasing the immune response.
  15. PD-L1 blockade enhanced the immune response , increase killing and increased production of cytokines,
  16. anti-tumor efficacy of anti-PD-1/Pd-L1
  17. Pancreatic and colono-rector — PD-L, PDL1, PDL2 — does not owrkd.
  18. In menaloma: PD-1 works better than CYLA-4
  19. Comparison of Targeted Therapy: BRAF TKI vs Chemo high % but short term
  20. Immunotherapy – applies several mechanism: pre-existing anti-therapy
  21. Immune desert: PD=L does not work for them
  23. PD blockage + nutrients and probiotic
  24. Tumor Genome Therapy
  25. Tumore Immuno-evasion Score
  26. Antigens for immune response – choose the ones
  27. 20PD-1 or PD-L1 drugs in development


  • Arlene Sharpe, the George Fabyan Professor of Comparative Pathology, Harvard Medical School; senior scientist, department of pathology, Brigham and Women’s Hospital – Multi-faceted Functionsof the PD-1 Pathway
  1. function of the pathway: control T cell activation and function of maintain immune tolerance
  2. protect tissues from damage by immune response
  3. T cell dysfunction during cancer anf viral infection
  4. protection from autoimmunity, inflammation,
  5. Mechanism by which PD-1 pathway inhibits anti-tumor immunity
  6. regulation of memoryT cell responce of PD-1
  7. PD-1 signaling inhibit anti-tumor immunity
  8. Compare: Mice lacking CD8-Cre- (0/5) cleared vs PD-1-/-5/5 – PD-1 DELETION: PARTIAL AND TIMED: DELETION OF PD-1 ON HALF OG TILS STARTING AT DAY 7 POSTTUMOR IMPLANTATION OF BOTH PD-1 AND PD-1 TILS: – Tamoxifen days 7-11
  9. Transcription profile: analysis of CD8+ TILs reveal altered metabolism: Fatty Acid Metabolism vs Oxidative Phosphorylation
  10. DOes metabolic shift: WIld type mouth vs PD-1-/_ P14: analyze Tumor cell killingPD-1-/- enhanced FAO increases CD8+ T cell tocicity
  11. Summary: T cell memory development and PD-1: T effectors vs T cell memory: Primary vs Secondary infection: In the absent of PD-1, CD8+ T cels show increase expansion of T cells
  12. INFLUENZA INFECTION: PRIMARY more virus in lung in PD-1 is lacking
  13. Acute infection: PD-1 controls memory T cell differentiation vs PD-1 increase expansion during effector phase BUT impaired persistence during memory phase: impaired cytokine production post re-challenge
  14. PD-1 immunotherapy work for patients with tumor: Recall Response and Primary response
  15. TIL density Primary vs Long term survivor – 5 days post tumor implantation – rechallenged long term survival
  16. Hot tumor vs Cold tumor – Deletion of PD-1 impairs T memory cell development


Opening Remarks: George Q. Daley, MD, PhD, DEAN, HMS

  • Scientific collaboration check point – avoid the body attacking itself, sabotaging the immune system
  • 1987 – Vaccine for HepB
  • Eight of the awardees got the Nobel Prize


Moderated by Joan Brugge, PhD, HMS, Prof. of Cell Biology

  • Evolution of concepts of Immunotherapy: William Coley’s Toxin streptoccocus skin infection.
  • 20th century: Immuno-surveilence, Immune response – field was dead in 1978 replaced by Immunotherapy
  • Rosenberg at NIH, high dose of costimulatory molecule prevented tumor reappearanceantbody induce tumor immunity–>> immune theraphy by check point receptor blockade – incidence of tumor in immune compromised mice – transfer T cell
  • T cell defficient, not completely defficient, self recognition of tumor,
  • suppress immmune – immune evasion
  • Michael Atkins, MD, Detupy Director, Georgetown-Lombardi, Comprehensive Cancer Center Clinical applications of Checkpoint inhibitors: Progress and Promise
  1. Overwhelm the Immune system, hide, subvert, Shield, defend-deactivating tumor trgeting T cells that ATTACK the immune system
  2. Immune system to TREAT the cancer
  3. Monotherapy – anti PD1/PD-L1: Antagonist activity
  4. Evading immune response: prostate, colcn
  5. MMR deficiency
  6. Nivolumab in relaped/Refractory HODGKIN LYMPHOMAS – over expression of PD-L1 and PDL2in Lymphomas
  7. 18 month survival better with Duv in Lung cancer stage 3 – anti PD-1- adjuvant therapy with broad effectiveness
  8. Biomarkers for pD-L1 Blockage
  9. ORR higher in PD-L1
  10. Improve Biomarkers: Clonality of T cells in Tumors
  11. T-effector Myeloid Inflammation Low – vs Hogh:
  12. Biomarker Model: Neoantigen burden vs Gene expression vs CD8+
  13. Tissue DIagnostic Labs: Tumor microenveironmenr
  14. Microbiome
  15. Combination: Nivo vs Nivo+Ipi is superior: DETERMINE WHEN TO STOP TREATMENT
  16. 15/16 stopped treatment – Treatment FREE SURVIVAL
  17. Sequencing with Standard Therapies
  18. Brain metastasis – Immune Oncology Therapy – crosses the BBB
  19. Less Toxic regimen, better toxicity management,
  20. Use Immuno therapy TFS
  21. combination – survival must be justified
  22. Goal: to make Cancer a curable disease vs cancer becoming a CHronic disease


Closing Remarks: George Q. Daley, MD, PhD, DEAN, HMS


The honorees will share a $500,000 prize and will be recognized at a day-long symposium on Oct. 5 at Harvard Medical School.

The Warren Alpert Foundation, in association with Harvard Medical School, honors trailblazing scientists whose work has led to the understanding, prevention, treatment or cure of human disease. The award recognizes seminal discoveries that hold the promise to change our understanding of disease or our ability to treat it.

“The discoveries honored by the Warren Alpert Foundation over the years are remarkable in their scope and potential,” said George Q. Daley, dean of Harvard Medical School. “The work of this year’s recipients is nothing short of breathtaking in its profound impact on medicine. These discoveries have reshaped our understanding of the body’s response to cancer and propelled our ability to treat several forms of this recalcitrant disease.”

The Warren Alpert Foundation Prize is given internationally. To date, the foundation has awarded nearly $4 million to 59 scientists. Since the award’s inception, eight honorees have also received a Nobel Prize.

“We commend these five scientists. Allison, Chen, Freeman, Honjoand Sharpe are indisputable standouts in the field of cancer immunology,” said Bevin Kaplan, director of the Warren Alpert Foundation. “Collectively, they are helping to turn the tide in the global fight against cancer. We couldn’t honor more worthy recipients for the Warren Alpert Foundation Prize.”

The 2017 award: Unraveling the mysterious interplay between cancer and immunity

Understanding how tumor cells sabotage the body’s immune defenses stems from the collective work of many scientists over many years and across multiple institutions.

Each of the five honorees identified key pieces of the puzzle.

The notion that cancer and immunity are closely connected and that a person’s immune defenses can be turned against cancer is at least a century old. However, the definitive proof and demonstration of the steps in this process were outlined through findings made by the five 2017 Warren Alpert prize recipients.

Under normal conditions, so-called checkpoint inhibitor molecules rein in the immune system to ensure that it does not attack the body’s own cells, tissues and organs. Building on each other’s work, the five award recipients demonstrated how this normal self-defense mechanism can be hijacked by tumors as a way to evade immune surveillance and dodge an attack. Subverting this mechanism allows cancer cells to survive and thrive.

A foundational discovery made in the 1980s elucidated the role of a molecule on the surface of T cells, the body’s elite assassins trained to seek, spot and destroy invaders.

A protein called CTLA-4 emerged as a key regulator of T cell behavior—one that signals to T cells the need to retreat from an attack. Experiments in mice lacking CTLA-4 and use of CTLA-4 antibodies demonstrated that absence of CTLA-4 or blocking its activity could lead to T cell activation and tumor destruction.

Subsequent work identified a different protein on the surface of T cells—PD-1—as another key regulator of T cell response. Mice lacking this protein developed an autoimmune disease as a result of aberrant T cell activity and over-inflammation.

Later on, scientists identified a molecule, B7-H1, subsequently renamed PD-L1, which binds to PD-1, clicking like a key in a lock. This was followed by the discovery of a second partner for PD-1—the molecule PD-L2—which also appeared to tame T-cell activity by binding to PD-1.

The identification of these molecules led to a set of studies showing that their presence on human and mouse tumors rendered the tumors resistant to immune eradication.

A series of experiments further elucidated just how tumors exploit the interaction between PD-1 and PD-L1 to survive. Specifically, some tumor cells appeared to express PD-L1, essentially “wrapping” themselves in it to avoid immune recognition and destruction.

Additional work demonstrated that using antibodies to block this interaction disarmed the tumors, rendering them vulnerable to immune destruction.

Collectively, the five scientists’ findings laid the foundation for antibody-based therapies that modulate the function of these molecules as a way to unleash the immune system against cancer cells.

Antibody therapy that targets CTLA-4 is currently approved by the FDA for the treatment of melanoma. PD-1/PD-L1 inhibitors have already shown efficacy in a broad range of cancers and have been approved by the FDA for the treatment of melanoma; kidney; lung; head and neck cancer; bladder cancer; some forms of colorectal cancer; Hodgkin lymphoma and Merkel cell carcinoma.

In their own words

“I am humbled to be included among the illustrious scientists who have been honored by the Warren Alpert Foundation for their contributions to the treatment and cure of human disease in its 30+ year history.  It is also recognition of the many investigators who have labored for decades to realize the promise of the immune system in treating cancer.”
        -James Allison

“The award is a great honor and a wonderful recognition of our work.”
         Lieping Chen

I am thrilled to have made a difference in the lives of cancer patients and to be recognized by fellow scientists for my part in the discovery of the PD-1/PD-L1 and PD-L2 pathway and its role in tumor immune evasion.  I am deeply honored to be a recipient of the Alpert Award and to be recognized for my part in the work that has led to effective cancer immunotherapy. The success of immunotherapy has unleashed the energies of a multitude of scientists to further advance this novel strategy.”
                                        -Gordon Freeman

I am extremely honored to receive the Warren Alpert Foundation Prize. I am very happy that our discovery of PD-1 in 1992 and subsequent 10-year basic research on PD-1 led to its clinical application as a novel cancer immunotherapy. I hope this development will encourage many scientists working in the basic biomedical field.”
-Tasuku Honjo

“I am truly honored to be a recipient of the Alpert Award. It is especially meaningful to be recognized by my colleagues for discoveries that helped define the biology of the CTLA-4 and PD-1 pathways. The clinical translation of our fundamental understanding of these pathways illustrates the value of basic science research, and I hope this inspires other scientists.”
-Arlene Sharpe

Previous winners

Last year’s award went to five scientists who were instrumental in the discovery and development of the CRISPR bacterial defense mechanism as a tool for gene editing. They were RodolpheBarrangou of North Carolina State University, Philippe Horvath of DuPont in Dangé-Saint-Romain, France, Jennifer Doudna of the University of California, Berkeley, Emmanuelle Charpentier of the Max Planck Institute for Infection Biology in Berlin and Umeå University in Sweden, and Virginijus Siksnys of the Institute of Biotechnology at Vilnius University in Lithuania.

Other past recipients include:

  • Tu Youyou of the China Academy of Chinese Medical Science, who went on to receive the 2015 Nobel Prize in Physiology or Medicine with two others, and Ruth and Victor Nussenzweig, of NYU Langone Medical Center, for their pioneering discoveries in chemistry and parasitology of malaria and the translation of their work into the development of drug therapies and an anti-malarial vaccine.
  • Oleh Hornykiewicz of the Medical University of Vienna and the University of Toronto; Roger Nicoll of the University of California, San Francisco; and Solomon Snyder of the Johns Hopkins University School of Medicine for research into neurotransmission and neurodegeneration.
  • David Botstein of Princeton University and Ronald Davis and David Hogness of Stanford University School of Medicine for contributions to the concepts and methods of creating a human genetic map.
  • Alain Carpentier of Hôpital Européen Georges-Pompidou in Paris and Robert Langer of MIT for innovations in bioengineering.
  • Harald zur Hausen and Lutz Gissmann of the German Cancer Research Center in Heidelberg for work on the human papillomavirus (HPV) and cancer of the cervix. Zur Hausenand others were honored with the Nobel Prize in Physiology or Medicine in 2008.

The Warren Alpert Foundation

Each year the Warren Alpert Foundation receives between 30 and 50 nominations from scientific leaders worldwide. Prize recipients are selected by the foundation’s scientific advisory board, which is composed of distinguished biomedical scientists and chaired by the dean of Harvard Medical School.

Warren Alpert (1920-2007), a native of Chelsea, Mass., established the prize in 1987 after reading about the development of a vaccine for hepatitis B. Alpert decided on the spot that he would like to reward such breakthroughs, so he picked up the phone and told the vaccine’s creator, Kenneth Murray of the University of Edinburgh, that he had won a prize. Alpert then set about creating the foundation.

To award subsequent prizes, Alpert asked Daniel Tosteson (1925-2009), then dean of Harvard Medical School, to convene a panel of experts to identify scientists from around the world whose research has had a direct impact on the treatment of disease.



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Reporter: Aviva Lev-Ari, PhD, RN

Each year the recipient(s) of the Warren Alpert Foundation Prize are recognized at a scientific symposium hosted by Harvard Medical School.

OCTOBER 6, 2016 –

1:30PM TO 5:30PM


The CRISPR/Cas9 Revolution and Gene Editing

In honor of Rodolphe Barrangou, Emmanuelle Charpentier,  Jennifer Doudna, Philippe Horvath, Viginijus Siksnys for remarkable contributions to the understanding of the CRISPR bacterial defense system and the revolutionary discovery that it can be adapted for genome editing.

Harvard Medical School
The Joseph B.Martin Conference Center
77 Avenue Louis Pasteur
Boston, MA 02115

Seating available on a first-come first served basis

Opening Remarks

Barbara J McNeil, MD, PhD, Acting Dean, HMS

Warren Alpert a very prestiguos Prize for advancements in Medicine, Treatment of disease and alleviation of suffering

Clifford Tabin, MD, Prof. of Genetics at HMS

  • CRISPR as regulatory system

Featured Speakers include:

Rodolphe Barrangou, PhD
Todd R. Klaenhammer Distinguished Scholar in Probiotics Research
North Carolina State University
CRISPR-mediated immunity in bacteria: discovery and applications


Philippe Horvath, PhD
Senior Scientist
CRISPR-mediated immunity in bacteria: discovery and applications

  • CRISPR-Cas: basics, history, applications, future
  • cas1 (larger number of spacers) and Cas 2 almost universal
  • DNA repeate in preKariotes, 2002 Milk coagulation, dairy industry – lactic acid, bacteriaphaging – failure of fermentation


  • 2005 outstanding spacer polymorphism
  • CRISPR genotype – phase sensitivity & resistance correlation
  • CRISPR – Mechanism of Action
  • 8/2005 Patent of bacteriaphage – Eureka:comercialization in 1990 200 sequence resistance to phage – Anti Phaging Hypothesis
  • certain spacers in genome cross immunity against the phage –
  • Spacers: engineeringCRISPR-encoded immunity resistence against phaging: ad spacer gain resistence
  • cas9 disruption >> loss of phage resistence in dairy bacteria
  • csn2 disruption -.. no subsequence acquisition of spacers
  • no phenotypic resistance loss
  • RNSi – A putative RNA-interference-based immune system
  • Science 2007
  • Discovery of the CRISPR motif (PAM): resistence in Streptococcus Thermophilus
  • Immunity is mediated by small CRISPR RNAs (crRNAs)
  • CRISPR Immunity – DNA encoded in bacteria
  • CRISPR/Cas bacterial immune system cleaves bacteriaphage and plasmid DNA, Nature 11/2010
  1. Immunization
  2. Interference with expression of immunity – with invading nucleus by viral DNA infection

Applications for CRISPR

  1. Bacterial strain typing
  2. natural vaccination against phages: CRISPerization (cultivation, plating)
  3. Natural genetc tagging
  • signature in the genome – genetic tag
  • strain identification
  • Patent for phage genome editing in 2009
  • Lethal self-targegting in bacteria programmable antimicrobial is death
  • genotype of interest selected
  • Agriculture applications: contamination in food, starters probiotics

Perspective on last Decade  

  • phage resistance phenotype
  • In silico & predictions in vitro
  • success in Crops, Food, Animals
  • Matters: IP (file for Patent, convert, publish), PR, Reg

Emmanuelle Charpentier, PhD
Prof. Dr.; Scientific Member of the Max Planck Society, Max Planck Director
Professor, Umeå University
The transformative genome engineering CRISPR-Cas9 technology: lessons learned from bacteria

  • Non-infectious Disease: Cancer, Heart Genetic, Brain
  • Infectious Diseases: Transmiable & Comnunicative
  1. Bacteria
  2. Viruses
  3. funcgi
  4. parasites
  • Enzyme Cas9 S. Pyogenes: Group A Strep
  • spacer acquisition – crRNA expression and maturationng CRISPR-CAS evolved into 6 types
  • Human Bacterial host
  • An mRNA : Type II CRISPR -Cas locus: TracrRNA – pre-crRNA
  • Cas9 requires tracrRNA:crRNA to cleave DNA
  • Genome editing with sequence specific nucleatease
  • RNA -programmable CRISPR -Cas9
  • Applications of CRISPR-Cas9 in human medicine: sequencing of Human genome – gene therapy to an organ, genetic predisposition of diseases
  • trcrRNA is associated to Type II CRISPR-Cas
  • Interchangeability among dual-RNA-Cas9 orthologs
  • Cpf1 – Type V-A
  • Adaptive Immune system
  • Mechnism of maturation of CRISPR-RNA

Jennifer Doudna, PhD
Li Ka Shing Chancellor’s Chair in Biomedical and Health Sciences/HHMI Investigator
University of California, Berkeley
The Future of Genome Engineering: Biology, Technology and Ethics

  • Biology
  • Technology  – Gene Editing
  • Ethics


  • Adaptation – acquire and maintain genetic memory Prokaryotic cells
  • crRNA Biogenesis
  • Interference
  • Supercoiled plasmid target helps for the integration reaction
  • Integration preceeds via a 3′-OH nucleophilic attack, 3′ – PO4
  • What directs Cas1-Cas2 to the leader side of CRISPR Loci
  • Integration Host Factor (IHF): alpha and beta
  • IHF is required for spacer acquisition in vivo
  • mechanism of spacer integration for DNA repair and repeat replication
  • Harness integrase for genomic tagging


  • CAS9 is a dual-RNA guided DNA Endonuclease
  • Cas9 programmed by single chimeric RNA
  • Most CISPR systems target dsDNA
  • PAM binding drives DNA target recognition: protospacer — PAM– dsDNA
  • C2c2 is an RNA-activated RNase: cis Cleavage vs trans Cleavage – used to detect specific RNA


  • Chromatin search
  • DNA repair
  • RNA targeting


  • CRISPR based white mushrooms programmed to resist browning
  • human gene modification


Virginijus Siksnys, PhD
Professor and Chief Scientist/Department Head, Institute of Biotechnology
Vilnius University
From mechanisms of microbial immunity to novel genome editing tools

  • bacteria can absorb interference
  • superinfection survival
  • defense islands in genomes
  • CCGG-family: specificity of restriction enzymes that recognize different nucleotides
  • meganucleases: ZFN, TALEN
  • CRISPR-Cas are transportable: CRISPR3 was transferred to e-Coli and plasmid
  • isolate Cas9 protein – RNA-guided endonuclease – adaptive immunity in bacteria
  • generate Cas9 variants
  • Cas9 – restriction enzyme – targeting 2 sites on a pUC18 plasmid
  • Cas9 specificityis encoded by crRNA: REases
  • Cas9- versatilegenome editing tool: induce DNA breaks, gene editing of Human cells, animals plants
  • Cas target is composite – >1000 Cas9 orthologues are known: 20 nt protospacer PAM sequence PAM Assay: PAM depends on Cas9 concentration
  • RNP assembly Cas9
  • Type II-CCRISPR-Cas for B. laterosporus
  • PAM preference for Blat Cas9
  • Maze genome
  • Off-target cleavage: role of PAM, PAM contribute to cleavage at off-target site: Stringent PAM restriction on Cas9



Invited Speakers:

Luhan Yang, PhD
Chief Scientific Officer
Rewriting the pig genome to transform Xenotransplantation

  • Organ transplantation unmet needs
  • natural bioreactor for organ transplants manufacturing

Obstacles for Xenotransplantation

viral transmission

  • immunological Incompatibility
  • New tools: CRISPR-Cas9 multiplexible genome engineering
  • Infectivity of virus  – Infectivity is real: gRNA to destroy catalytic PERVs
  • Eridicate of PERVs activates in PK15 cells
  • generate viable PERV free embryo
  • Genotyping of Clone 40
  • viral transmission

immunological Incompatibility

  • a disruptive technology across tissue and organ types
  • therapeutic applications


  • write the Genome
  • Next Generation of Gene Editing Tools


Austin Burt, PhD
Professor of Evolutionary Genetics
Imperial College London
Developing CRISPR-based gene drive for malaria control

  • Genetically MODIFICATION of the mosquito strains that brings Malaria to Humans
  • Driving Y chromosom – convert all population of mosquitos to MALE: don’t bite, don’t transmit and do not contribute to next generation
  • Homing: natural process endonuclease genes in many microbes
  • Find Gene needed for female fertility: Ovary  expression : sterile non-sterile
  • gene needed for vector competence
  • target gene validation: number of Larvae
  • CRISPR-based homing at target gene – Frequency
  • Issues arising form this approach: Resistance, ecological and biodiversity, Governance and acceptance, step by step development pathway


Warren Alpert Foundation Prize Recipients


For remarkable contributions to the understanding of the CRISPR bacterial defense system and the revolutionary discovery that it can be adapted for genome editing.


For their pioneering discoveries in chemistry and parasitology, and personal commitments to translate these into effective chemotherapeutic and vaccine-based approaches to control malaria – their collective work will impact millions of lives globally particularly in the developing countries.


For seminal contributions to our understanding of neurotransmission and neurodegeneration.


For their seminal contributions to concepts and methods of creating a genetic map in the human, and of positional cloning, leading to the identification of thousands of human disease genes and ushering in the era of human genetics.


For the discovery, preclinical and clinical development of bortezomib to FDA approval and front line therapy for the treatment of patients with multiple myeloma.


In recognition of their extraordinary contributions to medicine and innovations in bioengineering.


For the expansion and differentiation of human keratinocyte stem cells for permanent skin restoration in victims of extensive burns.


For the discovery, characterization and implementation of laser panretinal photo-coagulation, which is used to treat proliferative diabetic retinopathy.


For work leading to the development of a vaccine against human papillomavirus.


For their contribution to the development of the breast cancer therapy Herceptin, the first target-directed cancer treatment for solid tumors.


For discovering angiogenesis and its relationship to disease, and for championing the concept of anti-angiogenic therapies.


For her seminal contributions to the understanding of how the antitumor agent Taxol kills cancer cells.


For their pioneering work on the purification, characterization, and cloning of human interferon-alpha.


For his pioneering work in understanding the role of vitamin A supplementation in preventing blindness and life-threatening infections in children in the developing world.


For their pioneering work in cardiovascular research which has dramatically reduced the mortality rate for heart attacks.


For their research that contributed to the development of a drug that effectively treats chronic megelogenous leukemia and other forms of cancer.


For their research in the development of statins which lower the level of cholesterol in the heart.


For elucidating the pathway forming the leukotrienes and their role in bronchial asthma.


For their discovery of human immune deficiency virus (HIV).


For their discoveries of molecules that regulate the growth and differentiation of bone marrow cells in health and disease.


For the development of the lung surfactant used for treating pulmonary hyaline membrane disease.


For identifying Helicobacter pylori as the organism that causes gastric and duodenal ulcers.


For developing a complete description of thalassemia at the molecular level.


For discovering the enzymatic basis of Gaucher’s disease leading to its effective treatment.


For designing a powerful new approach to the treatment of high blood pressure and congestive heart failure.


For pioneering the use of DNA in the diagnosis of congenital anemias.


For defining the genetic basis of muscular dystrophy.

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