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Archive for the ‘cell-based therapy’ Category


Gene-editing Second International Summit in Hong Kong: George Church, “Let’s be quantitative before we start being accusatory”

 

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 11/30/2018

Gene editing takes a foreboding leap forward

He Jiankui. Photo: Zhang Wei/Chinese News Service/VCG via Getty Images

 

China is temporarily suspending the work of scientists who claimed twins were born after being genetically edited as embryos.

Why it matters: The scientific consensus is that gene editing embryos at this stage of science is “irresponsible.” But, while this particular experiment has not been verified, the fact is the technology is available to researchers, so there’s a growing call for international limitations on its use.

ICYMI: Chinese scientist He Jiankui announced earlier this week that twins were born after he used the gene-editing tool CRISPR-Cas9 to cut the CCR5 gene that’s known to play a role in HIV infection.

  • He stirred even more dismay when he mentioned the possibility of a second pregnancy.
  • China currently bans human implantation of gene-edited embryos. Its Ministry of Science and Technology is investigating the claims, per Xinhua.

There are concerns about the safety, efficacy and possible mosaicism, where a person can contain genes in both its edited and unedited forms, from cutting genes.

  • Editing embryos raises an even bigger concern: The genetic changes and all the unknowns around them can be passed down to future generations.

Between the lines: Not everyone viewed it as a complete disaster. For instance, Harvard Medical School’s George Daley suggested that it may be time to reconsider the massive amounts of research done over the past several years and look for plausible methods of moving forward.

What to watch: Scientists are cautious about predicting what the impact will be, in part because the details of this claim are thin. However, the debate is heating up and one concern is it will dampen important research.

  • Medical ethicist Jonathan Moreno from the University of Pennsylvania says the situation reminds him of other times in history where there were tremors in the science world, like the death of 18-year-old Jesse Gelsinger in 1999 from a gene therapy trial that led to years of diminished research.

The bottom line: The alarm over what could be next is real. But scientists hope the current debate will promote consensus on firm limits and promote transparency.

Go deeper:

SOURCE

From: Andrew Freedman <andrew.freedman@axios.com>

Date: Thursday, November 29, 2018 at 5:33 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Axios Science: About that climate report — Gene editing takes a foreboding step — Building in harms’ way

 

 

He Jiankui spoke at the second international summit on human genome editing in Hong Kong. (Alex Hofford/EPA-EFE/Shutterstock)

CRISPR-baby scientist faces the music

The scientist who claims to have helped produce the first people born with edited genomes faced a tough crowd yesterday at a gene-editing summit in Hong Kong. He Jiankui gave a 20-minute talk about his unpublished work in animals and humans before opening a 40-minute Q&A session (watch it here). He faced difficult questions about the ethics of his work and his choice to keep it mostly under wraps until after the babies were born, and left many unanswered.

Meanwhile, prominent geneticist George Church is one of the few scientists who seem to be looking on the bright side of He’s controversial claim. “Let’s be quantitative before we start being accusatory,” Church told Science. “As long as these are normal, healthy kids it’s going to be fine for the field and the family.”

Nature | 9 min read & Science | 6 min read

Read more: Genome-edited baby claim provokes international outcry

 

SOURCE

From: Nature Briefing <briefing@nature.com>

Reply-To: Nature Briefing <briefing@nature.com>

Date: Thursday, November 29, 2018 at 12:18 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: CRISPR-baby scientist faces the music at gene-editing summit

 

See

SAVE

The ethical red flags of genetically edited babies

Driving the news: Chinese scientist He Jiankui announced Sunday night that a pair of twin girls had been born from embryos he modified using the gene-editing tool known as CRISPR.

  • He hasn’t provided solid proof, but if it‘s true, it would be the first time the technology has been used to engineer a human.

What they’re saying: The inventors of CRISPR technology did not seem pleased with the development — one called for a moratorium on implantation edited embryos into potential mothers.

  • “I hope we will be more cautious in the next thing we try to do, and think more carefully about when you should use technology versus when you could use technology,” said Jessica Berg, a bioethicist at Case Western Reserve University.

Between the lines: Several specific factors in He’s work sent up ethical red flags.

  • Many scientists had assumed that, when this technology was first used in humans, it would edit out mutations tied to a single gene that were certain to cause a child pain and suffering once it was born — essentially, as a last resort.
  • But He used CRISPR to, as he put it, “close a door” that HIV could have one day traveled through. That has prompted some speculation that this project was more about testing the technology than serving an acute medical need.
  • “That should make us very uneasy about the whole situation,” Berg said. “Of all the things to have started with, it does make you a little suspicious about this particular choice.”

The intrigue: There’s a lot we still don’t know about He’s work, and that’s also contributing to an attitude of skepticism.

  • How many embryos did he edit and implant before these live births?
  • How will he know it worked? As the children age, they’ll likely have their blood drawn and those samples will be exposed to HIV in a lab, but researchers aren’t going to tell them to go out and have unprotected sex or use intravenous drugs — another reason HIV seems like an odd starting place for human gene editing.
  • How did this even happen? The university where He worked said he was on leave, and Chinese officials have said he’s under investigation. But gene editing is a pretty hard thing to freelance.

The other side: He defended his work in a video message, saying, “I understand my work will be controversial but I believe families need this technology and I’m willing to take the criticism for them.”

  • “Their parents don’t want a designer baby, just a child who won’t suffer from a disease which medicine can now prevent,” He said.

Yes, but: Now that this threshold may have been crossed, attempts to create “designer babies” — within the limitations of what CRISPR can do — probably aren’t far off, some experts fear.

  • There are “likely to be places that are less regulated than others, where people are going to attempt to see what they can do,” Berg said. “I wouldn’t say everything in the world has changed now, but it’s certainly the next step.”
SOURCE

https://www.axios.com/genetic-editing-baby-china-ethics-controversy-b33f8414-8b83-445c-bad5-d8407f8841f4.html

https://pharmaceuticalintelligence.com/2018/11/26/jennifer-doudna-and-npr-science-correspondent-joe-palca-several-interviews/

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LIVE 2018 The 21st Gabay Award to LORENZ STUDER, Memorial Sloan Kettering Cancer Center, contributions in stem cell biology and patient-specific, cell-based therapy

REAL TIME Reporter: Aviva Lev-Ari, PhD, RN

AWARD LECTURE

Tue., Oct. 9, 2018
4:00 PM
Shapiro Campus Center Theater
Brandeis University

CURRENT WINNER

lorenzstuder.jpgLORENZ STUDER

MACARTHUR FELLOWS PROGRAM

Lorenz Studer

Stem Cell Biologist | Class of 2015

Pioneering a new method for large-scale generation of dopaminergic neurons that could provide one of the first treatments for Parkinson’s disease and prove the broader feasibility of stem cell–based therapies for other neurological disorders.

https://www.macfound.org/fellows/947/

118 publications on PubMed

https://www.ncbi.nlm.nih.gov/pubmed/?term=LORENZ+STUDER

 

PRESIDING

Dagmar Ringe Professor of Biochemistry, Chemistry and Rosenstiel Basic Medical Sciences Research Center

WELCOME

Lisa Lynch Provost and Maurice B. Hexter Professor of Social and Economic Policy Brandeis University

 

RESPONSE Lorenz Studer, MD Director, Center for Stem Cell Biology Memorial Sloan Kettering Cancer Center Member, Developmental Biology Program Memorial Sloan Kettering Cancer Center

Fully defined protocol for all ectodermal lineage

  • Nervous system: Forebrain, Midbrain, Spinal cord:
  • CNS lineage to PNS Lineage
  • Excitatory cortical neurons
  • cortical interneurons Astrocytes
  • microglia
  • Age-reset disease – late-onset during reprogramming – Is age reversible?
  • Loss of age-related markers
  • iPSC-derived cells yield stage cell upon differentiation
  • In vitro differentiation techniques: 2D Directed Differentiation 3D- Organoids
  • Graded MORPHOGEN SIGNALING
  • DOXYCYLINE: ISHH-ORGANIZER – 5 discrete forebrain regions
  • Building Human brain cells in 2D and in 3D
  • Organized cells –>>>  directed organoids –>> Organized Organoids
  • Parkinson, 1817 – Essay on Shaky Palsy (Niagrostaterial pathway)
  • Genetics and related dysfunction: affecting PD
  • Charckot, 1889
  • PD – new approach following drugs and deep brain stimulation failure in advanced disease: Fetal tissue transplant trials: Fetal Grafting
  • graft-induced dyskinesia
  • Long term, 15 years positive effects
  • Stem-cell-based regenerative therapy could transform PD therapy
  • 1995  Fetal DA neuron grafting for PD in Switzerland
  • 1998 – midbrain stem cell derived DA neuron
  • 200-2003 – Stem cell in brain implantation in WashDC
  • 2011 – Behavioral assays that are restored in mice
  • Optogenetics: manipulating – Light on the brain – control animal’s neurons
  • MOA of Graft function
  • Dopamine neurons – Stratium area of the human brain
  • From bench to bedside – WNT boost enhances EN1 expression
  • Neuron melanin induction
  • Manufacturing and QA testing: GMP – Off the shelf Allogenic Product
  • 1,000 human dose equivalents
  • cryopreserve
  • MSK-DA01 is highly enriched for mDA neuron precursors without detectable hESC Contaminants
  • FDA feedback and final steps to IND – PRE-IND MEETING: 2014, 2016
  • GLP STUDIES:
  • TUMORIGENICITY, BIODISTRIBUTION AND TOXISITY
  • HISTOLOGY OF FINAL PRODUCT
  • CLINICAL TRIAL DESIGN – STEM-PD – MSK and Weill Cornell Medicine
  • HLA expression is absent in edited iPSC with expression of HLA-E to block NK clearance
  • FUTURE: CRISPR
  • ATLaS-PD – assessing the longitudinal Symptoms/signs to moderate of severe stage
  • Development of a new PD therapy from Pluripotent Stem Cells
  • BlueRock Therapeutics – MSK-PD – Start up – $240Million funding
  • Stem cell based dopamine therapy for PD
  • Immunosuppression for 12 months
  • defined levodopa response > 45% improvement
  • Conclusions
  • Cell banks for clinical trials
  • NY state Stem cell science consortia

http://www.brandeis.edu/rosenstiel/images/pdfs/gabbay21program.pdf

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