NAPIGEN is addressing unmet needs of future food supplies by creating hybrid crop plants to boost yields to unprecedented levels. Our company’s hybridization technology allows the production of non-GM hybrid seeds in crop plants that are currently mostly non-hybrid such as wheat.
The production of more efficient crop systems with our technology is also expected to help slow the rate of global deforestation by reducing the need for more farmland to meet the increasing demands for more cereal grains, thereby helping to protect our environment and climate.
The use of hybrid plants has dramatically changed corn yield in the past. The change was 8-fold when compared with pre-hybrid yield in 1930s (Figure 1). During the same time period, wheat, which largely is a non-hybrid crop, has only been blessed with less than a 3-fold change in yield increase. The world-wide acreage of hybrid wheat is very limited (less than 0.2%). However, the research shows that the current wheat hybrid plants already produce 15% more yield than inbred lines (1). This would correspond to 112 million tons and $23 billion more than the current wheat production per year. The effect of hybrid vigor is expected to be further improved by developing lines suitable for heterotic groups through classical breeding as was shown in the modern corn history (2).
(1) Longin, et al. (2012) Hybrid breeding in autogamous cereals. Theor. Appl. Genet. 125:1087-1096.
(2) Zhao, et al. (2015) Genome-based establishment of a high-yielding heterotic pattern for hybrid wheat breeding. PNAS 112: 15624-15629.
Figure 1. Improvement of corn and wheat yield in the last 140 years of the USA history. The yellow arrow shows the year when the hybrid seed system was introduced in corn breeding. The red arrow indicates the potential multifold yield gain obtained by the introduction of hybrid wheat. (Source: USDA)
While the vast majority of human DNA resides in the nucleus, a small amount of DNA is present
in the mitochondria. The genes present on mitochondrial DNA are essential for proper
functioning of cells as most cellular energy is produced in mitochondria. Mutations in
mitochondrial DNA are known to cause severe disorders in humans including but not limited to
degenerative and developmental disorders such as Kearns-Sayre syndrome and Leber’s
Hereditary Optic Neuropathy (see the UMDF website for more mitochondrial diseases).
Mitochondrial DNA mutations are also suggested to correlate with a predisposition for common
diseases like diabetes, Alzheimer disease, Parkinson’s disease and even for aging. Providing
ultimate cures for these diseases will require a method for gene editing within human
In recent years, CRISPR technology has been used to successfully edit genes on chromosomes
present in the cell nucleus. We have developed a CRISPR-based approach for editing of DNA
residing outside the nucleus. This approach has been successfully demonstrated in both yeast
mitochondria and algal chloroplasts (Yoo et al., 2020). Since the approach is simple and
effective in two unrelated species, it is expected to function in a wide range of organisms. We
are currently working to apply our technology to gene editing of human mitochondrial DNA.
The successful application of our technology to human cells is expected to open the door to the
use of CRISPR-based gene editing to repair deleterious mutations in mitochondrial DNA,
thereby providing potential cures for the corresponding human mitochondrial diseases.
Microorganisms such as yeast can be genetically engineered to produce desirable
compounds for industry. Examples include compounds for use in the areas of
food, fuel, and medicine. Production of such desirable compounds through
biotechnology often involves a multi-step process. Advantages could be realized
by having all reactions occur in the mitochondria. One way to achieve this goal is
to introduce the genes encoding all enzymes of the pathway into the
mitochondrial DNA instead of into the nuclear DNA, using our CRISPR-based
approach for editing of organellar DNA.
We plan to identify compounds of high value for production in the mitochondria
of microorganisms such as yeast. Having the genes for all enzymes of a pathway
localized in the mitochondria would provide higher local concentrations of both
the substrates and the relevant enzymes, resulting in higher enzymatic reaction
rates. Consequently, we expect localization to the mitochondria of all steps of a
desirable biochemical pathway to result in more efficient production and higher
yields of high-value industrial compounds.
Mitochondria provide fundamental advantages for industrial biotechnology. They
are the site of energy production in cells, full of high energy molecules like ATP
and acyl-CoA, and high levels of chemical reduction/oxidation potentials. We
intend to unleash the power of mitochondria for industrial biotechnology, as well.