International MPN News, Science & Opinion

Cold Spring Harbor Lab — Special Report on Gene Editing

October-November,  2015

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The Cold Harbor Spring Lab Meeting:  
Genome Engineering: The CRISPR/Cas Revolution

Zhenya Senyak

Jennifer Doudna Courtesy:CSHL

Jennifer Doudna                                     (Courtesy:CSHL)

It was another world, revolutionary, youthful and brash.

To be an observer at last week’s Cold Spring Harbor Laboratory’s CRISPR/Cas meeting is a bit like landing on a familiar but alien planet.The language is roughly similar with jarringly unfamiliar nouns and adjectives spicing the conversation but the culture of the molecular underground inhabited by the hundreds of young scientists gathered in small knots on the green lawns and broad terraces of CSHL could have arisen on a distant galaxy.

The conference, convened by Jennifer Doudna (UC Berkeley) and her colleagues Maria Jasin (Sloan Kettering) and Jonathan Weissman (UCSF) was billed as a presentation of current work in the CRISPR/Cas revolution. A couple of surprises at the meeting could prove revolutionary but in fact, the revolution is already well underway.

Gene editing from its earlier zinc finger nucleases and TALEN incarnations to today’s zippy, do-it-yourself CRISPR gene cut-and-paste kits, has  forever changed the face of the biological landscape and has already impacted the practice of medicine.

Three of the key founders of the CRISPR/Cas9 revolution were on hand:  Feng Zhang, of the Broad Institute, Doudna, and Emmanuelle Charpentier (Hannover Medical School ad Umea Centre).

 Who, after all, owns the rights to CRISPR/Cas9 editing? 

Only a few months back the dark intellectual property clouds over the CRISPR/Cas landscape seemed to threaten rapid development of the new technology as these three and their institutions filed contending  patent applications

Feng Zhang, MIT

Feng Zhang, MIT

and formed well-heeled and seemingly competitive corporations.

 CH 2 o lawnThat it hasn’t happened so far is a tribute to the open sharing of research, collegial relations and deposit of  plasmids (or bits of bacterial DNA and cloning data) into AddGene* by key players.   The opening of the meeting saw Charpentier warmly introduce Feng Zhang as Jennifer Doudna looked on.

A few minutes later, Feng would depart from his scheduled talk to introduce Cpf1, a new CRISPR enzyme — with the promise of still others to come.  It seemed likely to stimulate research while easing corporate tensions since now there would be more than one CRISPR tool.

The meeting was about science not intellectual property rights. For us,  looking for applications related to myeloproliferative neoplasms, the meeting was an extraordinary success.

Jacob Corn presented solid work on assymetric use of Cas9 enzymes — both wild type and catalytically altered  — to release one strand of DNA making it available for attachment to a complimentary single strand of DNA. This kind of HDR (homology direct repair) is considered more precise and open to rationally designed templates enhancing  therapeutic application.

Then there were the two exceptional breakthroughs. The painstaking discovery by the Feng Zhang lab of Cpf1,  a new class of CRISPR enzyme that is smaller, faster, more integrated and potentially more effective for MPN gene editing.. The  presentation  by Sangamo’s Fyodor Urnov dramatically proved the concept of using gene editing to correct genetic blood disease.

The meeting wasn’t confined to the large auditorium that held hundreds of participants and sported high tech audio-visiual equipment. It was everywhere on campus.CH Terrace RED Class  While profusely illustrated presentations were made on the auditorium stage based on a strict 15 minute limit, clusters of registrants gathered on the terrace watching  monitors broadcast the proceedings.  Beyond the terrace, the presentations were pumped throughout the Admin building of the lab spilling into the reading room, bookstore, library and café.

There were a few notable personal connections between synthetic biology and medicine.  Professor Min Wu, University of North Dakota, had come to Long Island to present his lab’s work on dampening host immunity by using CRISPR/Cas systems to target endogenous genes. We talked a bit about his work and our upcoming  CREATE seminar.

Later at lunch on the terrace, I heard ,”So tell me about CREATE.” Turning around I saw Min, sitting at the next table smiling,  ready to explore a potential clinical application.  Or at least talk about it.  Maybe not such an alien planet after all.

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Next:  

From Eugenics to Gene Editing: The dark beginnings of Cold Spring Harbor Labs. (More)

Feng Zhang and Cpf1 — Is this the next generation CRISPR? (Read)

Fyodor Urnov:  Gene editing for blood disease arrives. (More)

CREATE seminar explores MPN SCT gene editing. (View)

Jacob Corn joins MPN Genetics Scientific Board .(Read)

Letters:  Dollars for Docs — Dr. Jerry Spivak responds. (Read)

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