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  • Where We Are

MITOCHONDRIA - POWERHOUSE OF CELLS


We are Unleashing the 2 Billion Year-Old Power For:

Agriculture

Human Healthcare

Human Healthcare

Human Healthcare

Human Healthcare

Human Healthcare

Industrial Biotechnology

Industrial Biotechnology

Industrial Biotechnology

Fermentation

Industrial Biotechnology

Industrial Biotechnology

AGRICULTURE



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.

We need high-yielding crop plants to feed the world and save the environment

our planet is facing multiple challenges

Deforestation

Additional 3 billion people in 40 years

HYBRID CROPS

  

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)

HUMAN HEALTHCARE

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

mitochondria.


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.

industrial biotechnology

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.

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