Seed World

Three Reasons CRISPR Won’t Work 


Since the academic discovery of gene editing, farmers, researchers and all of agriculture have heard many promises about its potential. The trouble is, there’s all this excitement without taking a realistic look at what is needed to apply the technology in a way that it is in line with commercial needs.

We’re at a point that we need to figure out these challenges or CRISPR won’t work in the real world.

Next to the obvious regulatory and licensing hurdles, these challenges include considerable technical obstacles which still need to be overcome.

1. Transgenes are ineffective and cause regulation issues

At Hudson River Biotechnology, we’ve been working on a CRISPR workflow for four years. We gave our workflow the acronym TiGER. One of the biggest hurdles we worked through was finding a way to obtain a homogenous, edited plant within a commercially attractive timeline. 

This differs per crop, but in all cases meant stepping away from the use of transgenes, which is the primary academic way of applying CRISPR. Two great bonuses here are that our method is more controllable and therefore much more efficient and that without transgenes it can be applied in a much wider range of crops. 

2. Regeneration is difficult 

Whatever editing approach you work with, it goes hand in hand with the challenge of regenerating edited cells into a plant. Besides stepping away from transgenes, we’ve learned that the key to considerably reduce the time to market lies in single-cell regeneration. 

Single-cell regeneration means that after editing, individual protoplasts are regenerated into a whole plant. The benefit of this is that no additional measures have to be taken to guarantuee genetic stability. In other words, we can yield a transgene-free, genetically homogenous plant in one generation. We’ve adopted an effective, standardized single-cell regeneration approach and are making great strides with recalcitrant species by using smart delivery molecules, regeneration boosters and advanced materials adopted from the pharma world.

3. CRISPR protein can entail high licensing costs 

Cas9, while it made many headlines, is associated with a very expensive license. We needed to find something with high efficacy but a more affordable cost structure, which eventually brought us to the MAD7 protein. While there was less technical know-how for this protein, such as guide-design rules, and it is not commercially available, we tackled this by developing our own prorietery software and producing high-grade MAD7 in house. Thanks to this, we have been able to obtain very high editing effiencies and have managed precise gene editing, while using a protein that is commercially attractive for our clients. 

Next Steps

Still, strides need to be made to harnass CRISPR’s full potential. We still need to continue advancing the science behind CRISPR technologies and need to work diligently to inform consumers and politicians about what gene editing is. It’s not transgenic, and we need to be clear about that.

From a communications perspective, we need to be talking with people outside of agriculture more. I mentioned regulatory hurdles as one of the challenges to using CRISPR, and if we don’t explain science to the public, it could become an insurmountable challenge. We can’t let gene editing go down the same public perception route that GMOs did – we need this technology too much.

From a technical perspective, we need to spend time working with more crops and more genes. As you can imagine, we know a lot more about some crops – staples like corn, soybeans, etc. – than others, and it’s the same for their DNA. If we can do more research, we’ll better understand how genes work together and how to impact important traits such as disease and insect resistance.

We also need to enhance our CRISPR capabilities to do precise gene-editing and target complex traits. Theoretically, all positions in the genome can be customized. In practice however, some genomic sites are poorly edited and repair is rarely precise in plants. 

We continuously innovate to make precise editing of any position in the genome a reality. We also want to do this simultaneously at many different sites (multiplexing). This, in combination with more insight in how regulatory elements control (tissue specific) gene expression and how multiple genes conver complex traits, will allow us to truly harvest the full potential of CRIPSR. Transcending it from the blunt on-off switch that it is now, to a “volume regulator” that allows us to tune to any trait required and meet future crop challenges in this changing world.