By Dr. Karen Ring, Big3Bio Events Correspondent
It’s a pretty exciting time in the world of science.
Stem cell therapies are entering human trials, CAR-T cells are bringing new hope to immuno-oncology, and advancements in genome editing technologies have put gene therapy back on the table.
From a therapeutic perspective, the CRISPR/Cas9 genome editing system is one of the most promising technologies developed in the last five years. Dr. Jacob Corn, the scientific director of the Innovative Genomics Institute (IGI) at UC Berkeley, shed light on the rapidly evolving CRISPR/Cas9 revolution at the June BioScience Forum held in South San Francisco.
CRISPR (clustered regularly interspaced short palindromic repeats) and the CRISPR associated protein 9 (Cas9) were originally discovered in bacteria, as an immune defense system against foreign DNA from invading viruses. In simple terms, bacteria use the CRISPR system to identify and target foreign DNA and use the Cas9 nuclease to cleave the DNA so that it can no longer be a threat.
In 2012, scientists figured out a way to manipulate this system to target specific sequences of DNA in human cells. Not only were they able to target specific genomic sites by delivering engineered guide RNA sequences (which deliver the Cas9 complex to the desired spot), they were also able to use CRISPR/Cas9 to delete or edit DNA sequences and even introduce new genomic material. (For more details on the biology of this system, check out this review in Nature Biotechnology.)
CRISPR/Cas9 technology is a game-changer, and will accelerate advancements in biological research and medicine. Dr. Corn explained that currently, many of the genetic components that cause disease are known, but this knowledge has yet to produce effective cures. His dream is to actually do something about this issue by using the power of CRISPR/Cas9 targeted genome editing. He focused his talk on how he and other researchers at IGI will achieve this dream.
Achieving the Dream
Dr. Corn began by giving a historical background on genome editing, and pointed out that currently “genomes are better read than edited.” This statement was a nod to the major advancements in next generation sequencing technologies and an acknowledgement of the hurdles that genomic editing has faced. Earlier methods of genome editing include zinc finger nucleases (ZFNs) and TALENs, but these methods have proven to be inefficient, expensive and time-consuming.
Dr. Corn emphasized that the recent discovery of CRISPR/Cas9 has tipped the scales and efficient, targeted genome editing is becoming a reality.
He described CRISPR/Cas9 as a fast and cost effective genome editing technology that anyone can use successfully. He even shared that an undergraduate in his lab who had never touched a pipette before learned how to use CRISPR to generate gene knockout cell lines in a month! This is a pretty impressive feat and speaks to how approachable and effective this technology is.
He focused on recent achievements in the CRISPR/Cas9 field and the impact that this technology will have in the short and long-term. Here are the main take away points:
- CRISPR/Cas9 is a great tool for modeling cancer. Using CRISPR, scientists can generate large genomic deletions that mimic the chromosomal translocations that occur in cancer cells. Already in vivo mouse models of human cancer have been generated using this technology.
- CRISPR technology has been used for large-scale, high-throughput functional screens. Multiplexed guide RNA libraries allow for whole genome pooled screens and the generation of a panel of genetic knockout cell lines for drug and phenotypic screening.
- Scientists have used CRISPR/Cas9 to edit DNA in mouse and human zygotes. This has drastically shortened the time it takes to generate of mutant mouse models and even allows for the generation of models with multiple genetic mutations in a single step. A more recent study published in April was able to genetically edit human 3PN (tripronuclear) zygotes. Dr. Corn emphasized that while this is a major break through, scientists need to discuss the ethical implications that arise when considering genetic modification of human zygotes.
- The immunology field has benefitted dramatically from CRISPR/Cas9 technology. The Marson lab at UCSF has successfully modified primary human T-cells using CRISPR/Cas9. This result has huge implications for CAR-T cell therapy. Dr. Corn also mentioned an ongoing clinical project at IGI involving ex vivo editing of hematopoietic stem cells for autologous transplantation in patients with sickle cell disease.
Dr. Corn ended the night by discussing the impact that the CRISPR/Cas9 revolution will have on the scientific community and human health. In the short term, CRISPR/Cas9 will make it easier to generate knockout human cell lines and animal models for phenotypic screening and will allow for better safety models (such as humanized rats) for therapeutic development. In the long term, CRISPR/Cas9 can be used to develop in vivo therapies that target specific tissues or even post mitotic cells (cells that no longer divide). This could dramatically change how we treat patients with degenerative diseases like muscular dystrophy and Alzheimer’s disease.
For a more coverage on CRISPR/Cas9 check out these articles:
- Tech Crunch: The Genome Engineering Revolution
- Science: The CRISPR Revolution (Special Collection)
- Nature: CRISPR leaps from lab to industry
The July event BioScience Forum features Thorsten Melcher from J&J Innovation. More information here.