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Analysis: human immunity to Cas9 bigger #CRISPR therapeutic hurdle than off-targets?

April 6, 2018 / Professor Paul Knoepfler, Ph.D. / 1 Comment

Some in CRISPR-Cas9-land who are focused on potential future clinical applications are kind of rejoicing or at least sighing a breath of relief. This upbeat swing in the atmosphere (from investors especially) was sparked by retraction of that paper, the one initially reporting tons of supposed off-target CRISPR-Cas9 activity in mice, which turned out to be a “nothing […]

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Highlights #FOGM18 Day 1: Data from Ancient Dirt, Genomics Dilemmas, CAR-T, & CRISPR

March 2, 2018 / Professor Paul Knoepfler, Ph.D. / 2 Comments

There are many genomics meetings out there these days, but The Future of Genomic Medicine meeting (#FOGM18) at Scripps in La Jolla is one of my favorites. This meeting is uniquely empowering. The people and the talks combine for a one-of-a-kind experience. The venue doesn’t hurt either at the Scripps Seaside Forum. The evening before the meeting

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Journal club: Jaenisch lab paper on epigenetic CRISPR-Cas9 rescue of Fragile X in a dish

February 26, 2018 / Professor Paul Knoepfler, Ph.D. / 3 Comments

Liu-et-al.-Figure-6C-Fragile-X-CRISPR-Cell-e1519673510685

There’s much more to CRISPR-Cas9 than just gene editing and a new paper from the lab of Rudy Jaenisch in Cell highlights that in an exciting way. It reports epigenetic reversal of a Fragile X Syndrome phenotype in induced pluripotent stem cell (IPSC) neurons. Fragile X Syndrome is a neurological disorder in boys resulting from CGG repeat

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Why we shouldn’t view the human embryo as a gizmo even in the CRISPR era

January 31, 2018 / Professor Paul Knoepfler, Ph.D. / 4 Comments

My first job in science was as a lab technician at UCSD School of Medicine and a big part of that job was growing cells called HUVECs or human umbilical vein endothelial cells. We isolated and grew the HUVECs from umbilical cords that we retrieved from the maternity ward of the UCSD hospital, which first

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CRISPR to make IPS cells: review of new Ding lab paper

January 21, 2018 / Professor Paul Knoepfler, Ph.D. / 4 Comments

CRISPR and IPS cells are two of my favorite things so when they come together as in a cool, new paper from Sheng Ding’s lab, I’m excited to read it and curious as to what the scoop is. Since 2006-2007 when mouse and human reprogramming were first reported, many different methods have been explored to

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Keep calm & CRISPR on: perspectives on report of human Cas9 immunity

January 9, 2018 / Professor Paul Knoepfler, Ph.D. / 7 Comments

The news that CRISPR-Cas9 gene editing in its current form may not work in a substantial fraction of people due to many of us having immunity to Cas9 came as a shock to many, but if you think about it, maybe it’s not so surprising. I don’t see it as the end of the world. A (preprint) from

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7 tech hurdles to human germline CRISPR

November 6, 2017 / Professor Paul Knoepfler, Ph.D.

Human germline CRISPR raises major bioethical considerations, but what about technical issues? Setting aside the many ethical issue about the general idea of human modification itself, could this really work? Yes in theory it could, but there are some very tough technological challenges that could and likely would cause failures or unacceptable outcomes at many steps

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Countering that Pro-Heritable Human CRISPR WSJ Piece

October 22, 2017 / Professor Paul Knoepfler, Ph.D. / 9 Comments

It’s germline, heritable human CRISPR time, right? Wrong. But the particularly enthusiastic supporters of heritable human CRISPR often cite hypothetical benefits in glowing terms, but either don’t mention risks or strongly downplay them. These fans also tend to leave alternative, proven and safe technologies such as preimplantation genetic diagnosis (PGD) out of the discussion or

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Why Mitalipov’s ‘magic’ room for human embryo CRISPR may give us pause

October 3, 2017 / Professor Paul Knoepfler, Ph.D. / 7 Comments

The debate over whether the main conclusions of the Nature paper on human embryo CRISPR led by Shoukhrat Mitalipov’s lab at Oregon Health Sciences University (OHSU) are correct remains unresolved. Note that Nature just added an editorial alert just above the references section to their paper: “Updated online 02 October 2017. Editorial Note: Readers are alerted that some

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Science hype award for worst CRISPR headline

September 24, 2017 / Professor Paul Knoepfler, Ph.D. / 2 Comments

Science hype is one of the more troublesome issues in our field today especially at its interface with the media, and unfortunately a ‘great’ example of that came this past week in a headline from the Daily Mail on the new CRISPR of human embryos paper from Kathy Niakan’s group in the UK. Although Niakan’s

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