Paper on 1st use of CRISPR in normal human embryos: problems remain

The first report of the use of CRISPR gene editing in normal human embryos was published today as a short paper from a team in China. There have been rumors for over a year that more CRISPR human embryo papers were coming including some using normal embryos. Here’s one and we can now expect more even as there remain scientific and ethical discussions about this kind of work.

CRISPR human embryo Tang et al

Figure 1b, Tang, et al. CRISPR of 3PN embryos.

You can read the actual paper Tang, et al. here, published in the journal Molecular Genetics & Genomics. This work was published by Jianqiao Liu’s lab. They attempted editing in both abnormal (3PN)  and normal human embryos. Figure 1b from the paper of CRISPR’d nonviable embryos, is shown above.

Some proper gene editing was reportedly evident after injection of CRISPR in normal human zygotes. Further, the efficiency of the genetic modification of the CRISPR’d embryos was higher in the context of using healthy embryos than in previous reports that used nonviable embryos and in the nonviable embryos used in this same study.

But major problems remained such as incorrect editing (making of a disruptive Indel rather than a correction) and quite a bit of mosaicism. While they did not detect off-target effects at a handful of specific predicted possible off-target sites or by some WGS, such sites could still exist. Continue reading

CRISPR Update: Patents, Embryos, & IPOs, oh my

It’s been a busy few weeks for the CRISPR arena so I’ve made a CRISPR Update. I’ve listed below links to some commentaries and key developments.Joanne Manaster

 

Fun Video interview on Read Science! with Joanne Manaster on my new book on CRISPR in humans, GMO Sapiens.

CRISPR: Pursuit of profit poisons collaborationNature piece by Jacob Sherkow

HIV Fights Off CRISPR Gene-Editing Attack. HIV adapts when CRISPR attacks.

2nd group CRISPR’s human embryos and things don’t go well. More Indels than precise gene edits, mosaicism and more.

CRISPR biotech Intellia strikes licensing deal with Regeneron, readies IPO. It’s interesting that there are these CRISPR IPO’s when the CRISPR patent situation remains entirely up in the air.

George Church versus Marcy Darnovksy on human modification in the WSJ

CRISPR/Cas9 Used to Create Knockout Chickens. Bock bock adoodle moo

Top 10 list of CRISPR predictions for New Year

CRISPR predictionsCRISPR is the hottest new biotechnology and the top development of 2015 according to Science Magazine.

What will the new year of 2016 bring on the CRISPR front? It’s clear there will be more meetings on CRISPR ethics and policy (heck, we are having one right here at UC Davis on May 26), but what else is coming?

Below are my top 10 CRISPR predictions for the new year in no particular order. What are your CRISPR predictions? For more on my thinking on CRISPR and the future, also please take a look at my new book, GMO Sapiens and for the extreme case of what could go wrong see my TED talk.

The CRISPR predictions.

  • The Noah’s arc of CRISPR-y critters continues to fill. We’ll see the trend of CRISPR’d animals accelerate. For more on CRISPR’d animals see here. The range of unusual GM animals such as super-muscled, glowing, or pint-sized critters will grow larger in 2016.
  • More CRISPR’ing of human embryos. At least one and probably more new human embryo editing papers go beyond the one published this year. 2016 will bring higher quality published data on human embryo modification with better success than the first paper in 2015. This double-edged sword means the technology is improving and that is great, but at the same time it may encourage some to be bolder in calling for human modification (see below).
  • Advocates for human editing push against restrictions. As we saw in 2015 with some voices for allowing or at least not restricting various forms of human genetic modification (George Church, Steven Pinker, Julian Savulescu, Nita FarahanyJohn Harris, and others) 2016 will bring more assertive calls for avoiding restrictions on or actively going forward with human genetic modification.
  • Editing of viable human embryos. We’ll see some indications of genetic modification specifically of viable human embryos. With the current trends it is likely that someone will report modification of viable human embryos rather than only focusing on nonviable ones as in that first paper from 2015.
  • CRISPR gets even better. More papers on making CRISPR systems that have better specifically and hence lower off-target effects in cells and model organisms. There will be more reports of CRISPR used to make precise mutations, not just INDELs.
  • Standardization of CRISPR evaluation. Calls grow for standardization of how to evaluate how well CRISPR is working. Right now it can be a challenge to compare, for instance, efficiency and specificity in two different CRISPR papers.
  • Human genetic modification laws. Talk grows at the federal and possibly state levels in the US regarding legislation on human genetic modification. This goes beyond the temporary restrictions in the appropriations bill passed in late 2015. Such legal restrictions, if enacted, may put a chill on important CRISPR experiments in the lab.
  • Gene drive accelerates. We’ll see more interest in nuclease-driven gene drive. I hope this is next part is wrong, but it is possible a gene drive organism may exist outside of a lab whether intentional (e.g. an experiment with malaria) or due to accidental release. For more on the power of and concerns over gene drive see here.
  • Patent progress? We’ll hear some news on the patent dispute over CRISPR.
  • Going germ. Data on human germ cell (sperm or egg, primordial germ cell) editing are published. Talk grows of the possibility of using CRISPR’d human germ cells as an alternative to editing one-cell embryos.

GOP Congress seeks ban on CRISPR of human embryos

crispr nihGOP members of Congress want a ban on CRISPR of human embryos. They are moving to block genetic modification of human embryos using the new CRISPR gene editing technology.

The new proposed spending bill part way through the approval process with the nugget of good news of a possible NIH spending boost after many years of losing ground against inflation, reportedly also contains language to block gene editing of apparently any human embryos even just for research. Update: More recent interpretations of the bill including by Hank Greely (quoted in media and in his comment on this post)  read things such that human embryo research in the lab using CRISPR would be permitted. Material in this post has been edited to reflect this additional new context.

The funding for the coming year for biomedical research thus would be restricted such that none of it could be used, “in research in which a human embryo is intentionally created or modified to include a heritable genetic modification.”

Bioethicist Art Caplan was quoted in a Business Insider piece that this ban is a bad idea since it would drive the research into strictly privately funded research labs…perhaps with less transparency.

I support continued research including in some limited cases using CRISPR in human embryos with appropriate ethical and institutional oversight and training for the researchers involved. You can see more on my views in my TED talk (also pasted above) and in my new book on human genetic modification.

Politico, reporting on the same development made it sound like the provision might be more specific just to the clinical sphere:

“the spending bill also blocks gene editing — denying the FDA any funds to review or approve clinical research in which a human embryo is intentionally created or modified to include a heritable genetic modification.”.

To be clear, I do support a moratorium on genetic modification of embryos, but only specifically when there is the intent to use them in a clinical setting to create genetically modified people. The Washington DC summit at the National Academy of Sciences two weeks ago (#GeneEditSummit) discouraged heritable clinic applications of CRISPR in humans, but did not go so far as to propose a moratorium.