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As the world continues to strive under this challenging time, the Department of Science and Technology-Biosafety Committee (DOST-BC) continues its mission to ensure that the best available science is utilized in assessing the safety of plants and products derived from modern biotechnology. With this, the Committee invited Dr. Daniel Voytas to talk on gene editing in its DOST-BC monthly webinar last March 22, 2022 via Zoom platform.

Dr. Daniel Voytas is a Professor in the Department of Genetics, Cell Biology and Development and the Director of the Center for Precision Plant Genomics at the University of Minnesota. Dr. Voytas graduated from Harvard College in 1984 and received his Ph.D. from Harvard Medical School in 1990. He conducted postdoctoral research at Johns Hopkins University School of Medicine where he was a fellow of the Life Science Research Foundation. Prior to joining the University of Minnesota in 2008, Dr. Voytas was a professor at Iowa State University.  Dr. Voytas’ research focuses on developing methods to edit plant genomes. His laboratory developed a powerful genome editing reagent – Transcription Activator-Like Effector Nucleases (TALENs) – which was heralded by Science magazine as one of the top ten scientific breakthroughs of 2012.  Dr. Voytas’ lab is currently optimizing methods for efficiently making targeted genome modifications in a variety of plant species to advance basic biology and develop new crop varieties.  In addition to his position at the University of Minnesota, Dr. Voytas co-founded Calyxt, an agricultural biotechnology company that uses gene editing for crop improvement. He currently serves as Chair of the Science Advisory Board for Calyxt.  In 2019, Dr. Voytas was elected to the National Academy of Sciences.

Dr. Voytas started his presentation by citing four (4) techniques on how to capture genetic variation for crop improvement. 

First is cross breeding which is the traditional technique usually performed to cross-breed a susceptible variety to a disease resistant variety followed by 5-7 cycles of backcrossing.  Backcrossing is a process of mating a hybrid organism (offspring of genetically unlike parents) with one of its parents or with an organism genetically similar to the parent. The backcross is useful in genetics studies for isolating (separating out) certain characteristics in a related group of animals or plants. This process however, would take 8-10 years to create an elite variety with disease resistance crop. Another technique is mutation breeding which allows disease susceptible elite variety be subjected to mutagens (i.e. gamma rays, chemical mutagens, etc.) and grow large populations of these mutagenize plants to identify those who acquired the disease resistant variant. This however, are inherently random and non-specific and would take the same amount of time as traditional cross breeding technique would take. When biotechnology came to the floor, it enables the introduction of genes from other organisms, for example, from rice or wheat to be introduced to the disease susceptible variety and create a transgenic plant that had a trait of interest.  But because the trait is encoded by other organisms and there is no control on where the foreign DNA will land in the genome, this became the subject to governmental regulation and this limit the widespread use of Transgene Breeding. These scientific techniques paved the way to gene editing where it is able to identify the gene that confers resistant to a disease and make precise alteration to the genome in order to achieve the elite variety with disease resistance product. Also, genome editing would only take 4-6 years which is significantly faster than the previous techniques.

Dr. Voytas also presented the different gene editing platforms such as Meganucleases, Zinc-Finger Nucleases, and TALENs. These are proteins that recognize a specific DNA sequence and can find precise sequences within complex genomes. Once these proteins land at their targets, they create a double strand break in the DNA. Another gene editing platform is CRISPR/Cas, which, instead of a protein recognition domain, it encodes an RNA that based pairs with the target and then the nucleus creates that targeted break. The goal is also to create a double strand break.

A double-strand DNA break (DSB) occurs or arises when both strands of the DNA duplex are severed, often as the result of ionizing radiation.

Dr. Voytas made an illustration of harnessing DNA DSB repair pathways. He showed in his illustration that when a sequence genome makes a break using CRISPR, the broken chromosome can be rejoined, a process called Non-Homologous End Joining (NHEJ). This however, is imprecise as it loses the information of the break side. On the other-hand, Homologous Recombination (HR) can make the broken chromosome copy the related information and insert this information or replace the sequence within the genome at a very precise alteration.

He mentioned soybean as an example of NHEJ and is a product registered under Calyx. It is the first genome-edited crop which entered the food supply

The fatty acid composition of soybean was altered because of its low monounsaturated fats in contrast to other healthy oil like canola, olive, and sunflower. In the past, soybean oil is chemically treated through a process called hydrogeneration. Where hydrogenation increases the monounsaturated fats, extends the shelf life and heat stability of the soybean, this application would also increase the trans-fat. Despite the promising result, hydrogeneration became a non-factor since this application would allow an increase in trans-fatty acid which is banned in the United States.

As Calyxt recognized its effect on the soybean farmers, they began applying gene editing to change the fatty acid composition of the oil.

With this new scientific application, in 2015, Calyxt consulted the United States Department of Agriculture (USDA) to see if they can reproduce more of these crops in the field, ant they were given approval. In the present regulatory framework of the US Department of Agriculture, it does not regulate genes that are activated via mutation. The USDA regulation also stipulates that they will also not regulate plants with single base modification and plants in which gene editing is used to introduced an allele (gene variant) that already exists in nature in a sexually compatible organism.

Dr. Voytas also presented their project on herbicide tolerant cassava using homologus recombination which was carried out in the University of Minnesota.

Recognizing that cassava is one of the main sources of carbohydrate in some part in Africa, the productivity of cassava, however, is hampered by weeds. This circumstance forced children to clean out weeds in the field. Seeing this situation, the Bill and Melinda Gates Foundation sponsored the project for two reasons: they wanted to help increase the yield of cassava, at same time prevent children in laboring in the field.

In closing, Dr. Voytas stated that this technology is progressing at a rapid state because of its potential in creating more complex traits and he is looking forward to deploy this technology at its full extent. #