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© Image 2014 Wikipedia
CRISPR is a bacterial immune system that has been repurposed as a precise molecular find-and-replace tool for genome editing. Dozens of variants of the CRISPR system exist, allowing scientists to find and modify any genetic element, in any cell, in any way. The applications of CRISPR genome editing are diverse as the tool lets researchers mutate any gene in order to elucidate its function, or modify a trait in an advantageous way. 

First used in 2013, the CRISPR method for genome editing is now revolutionizing genetic engineering thanks to its simplicity, precision and cost-effectiveness - an experiment cost's around $ 60 in materials. The core principle of the CRISPR system involves programming an enzyme to bind to a specific section of an organism's genome, cut it, and repair it. The technique is important in loss-of-function, gain-of-function, preclinical and clinical research. 

Why Edit Genomes?

Before jumping into where CRISPR comes from and how it works, it is helpful to first understand why editing genes is useful. There are six main reasons why scientists would wish to modify a gene:

  1. To understand the role that specific mutations in specific genes influence a particular trait of an organism
  2. To create new traits that do not exist in nature 
  3. To recreate known stable mutations in cell lines that can serve as models of a particular disease 
  4. To create stable mutations in whole organisms (plants / animals) and create strains that can be used in research or commerce
  5. To create gene therapies in order to treat or prevent congenital diseases, infections, or cancers
  6. To create gene drives that can modify populations of organisms in a specific way (highly experimental at the time of writing)

This list is not exhaustive, and the applications of genome editing grow more diverse every day. In summary however, genome editing is valued for its ability to precisely modify one or more genetic elements in an organism in order to elucidate its function, or modify a trait in an advantageous way.

Why use CRISPR for Genome Editing?


 

CRISPR & Cas9 concept and vision © 2015 SynBio.Info

It was only very recently that scientists figured out that naturally-occurring bacterial CRISPR systems could be repurposed into precision-guided genome-editing tools. The value biologists see in the CRISPR system is its programmability, precision, and ease of use
compared with previous genome editing technologies like Zinc Finger Nucleases (ZFNs) and Transcription-factor-like-engineered-nucleases (TALENs). 

As described elsewhere, DNA codes for RNA, and RNA codes for proteins. The functional components of CRISPR can be shuttled from one organism to almost any other using a variety of synthetic, recombinant and other biotechnological procedures which allow modern biologists to boot up foreign or new programs in a variety of organisms using CRISPR vectors.  These plasmids or vectors can be synthesised chemically, or assembled using standard molecular cloning techniques, or commercially available kits.

 

CRISPR vectors are widely available and they are fairly uniform in their construction, generally only requiring a guide or protospacer sequence to be inserted into them, in order to become fully functional. This means that a laboratory only needs one CRISPR vector in order to begin editing any gene in the specific organism that the vector is optimised for.

Each time the lab wants to modify a gene, all they need to do is purchase synthetic DNA, insert it into the right section of the vector using standard PCR or cloning techniques (very low-tech for most labs) and transform it into the cell of interest (also very low-tech). While many inside and outside the biotech field refer to the low costs of CRISPR (starting at $60 for a vector), this factoid masks the requirement to have a laboratory with the right equipment and staffed by personnel with the capabilities to use it, meaning that the actual costs and setup requirements are much more than this.

Nevertheless, older genome editing technologies (ZFNs and TALENs) are far more difficult to use, and essentially required a laboratory to invest in high-tech protein engineering facilities in order to create a custom nuclease protein every time they want to edit a single gene. This made the older genome editing technologies far more long-winded and expensive to use when compared with CRISPR.

In any case, CRISPR genome editing is incredibly versatile - by changing a guide sequence, or changing the nuclease used (as each nuclease has a different PAM), it is possible to find a way of targeting almost any gene in any organism. TALENs and ZFNs on the other hand can only be targeted towards specific sequences, and their coverage of a genome is limited. For CRISPR, as scientists discover or engineer more nucleases, it is likely only a matter of time before all genomes have total coverage of possible cut sites, enabling all areas of the genome to be edited with high fidelity. 

What are the Applications of CRISPR?

Six general application's of CRISPR

  1. To understand the role that specific mutations in specific genes influence a particular trait of an organism
  2. To create new traits that do not exist in nature 
  3. To recreate known stable mutations in cell lines that can serve as models of a particular disease 
  4. To create stable mutations in whole organisms (plants / animals) and create strains that can be used in research or commerce
  5. To create gene therapies in order to treat or prevent congenital diseases, infections, or cancers
  6. To create gene drives that can modify populations of organisms in a specific way (highly experimental at the time of writing)

 

Applications of the CRISPR/Cas9 System

The CRSIPR/Cas9 System is only developed in 2012, so there isn't anything on the market yet that was developed with this phenomenal gene editing technique. It is mostly used by academic labs and commercial life science companies for basic and applied research. However, the outlook of this work promising:

Public Discussion about CRISPR

CRISPR genome editing has received a great deal of press and public attention in the last year, and discussion of its implications is being had in a variety of media and forums, such as Wired, MIT Technology Review, Radiolab and even SXSW Interactive 2016:

Note: SynBio.info will post a video of this discussion for public benefit ASAP. 

Who is involved? 

There are around 50.000 researchers world wide already working with this technology - here are a few of the most notable labs and companies:

Research Groups of Note

Many research groups have led the way in the development and uptake of CRISPR genome editing technologies and their applicaitons:

Companies of Note

A number of companies have formed or adopted CRISPR technology in order to unlock its true potential across a variety of applications:

  • Editas Medicine - a therapeutics company developing new ways of treating genetic diseases, cancer and infectious disease
  • Caribou Bioscience - a platform company developing tools for CRISPR applications in industrial and agricultural biotechnology
  • Intellia Therapeutics - a therapeutics company developing new ways of treating and preventing rare genetic disease
  • Desktop Genetics - a software company building an AI that can identify optimal techniques to edit any gene in any organism
  • Eligo Bioscience - a company developing highly targeted antimicrobial agents against drug-resistant infection
  • Horizon Discovery - a biotechnology company offering a variety of genome editing services for pharmaceutical clients 
  • Addgene - a non-profit plasmid repository that has been instrumental in shipping CRISPR vectors to thousands of academic labs across the world

View full profile Edward Perello from London

Edward Perello is the founder of Desktop Genetics, a company at the forefront of CRISPR genome editing technology. His team is working to provide researchers with access to state of the art genome engineering capabilities from their computers and create an AI that can predict optimal genome editing solutions in any organism.

Edward is a SynBio LEAP fellow working to get more non-biologists into the field.

https://www.deskgen.com/

 


What do you think?

About the authors

View full profile Jérôme Lutz from Berlin & Munich, Germany

I like to share the great things I discover daily while researching and working in the field of Synthetic Biology.

When I talk to people about it, they often refer to Science Fiction. However, when I send them links to this wiki and they read through those pages, they start understanding that this is real and it's happening right now.

View full profile Jake Curtis from London

I am a student at Cambridge University who has just finished a BA in Natural Sciences, focusing on Genetics in my third year. I am now studying for an MSc in Systems Biology.

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