Genetic Modification in Industry and Agriculture: GMOs, Cloning and CRISPR

Already in your kitchen and your medicine cabinet

Most canola grown on the Prairies is genetically modified. Much of the cheese in stores is made with an enzyme produced by genetically engineered microbes. Insulin, many vaccines and several cancer drugs are made in engineered cells. And since late 2023, an approved treatment for sickle cell disease has used patients' own gene-edited blood stem cells.

Expectation D3.5 asks you to describe examples of genetic modification and explain how it is applied in industry and agriculture. This lesson puts the tools from the last two lessons to work. The next lesson weighs the social, ethical and legal questions they raise.

Industry: engineered cells as factories

• Medicines. After insulin (1982), engineered bacteria, yeast and mammalian cells began producing human growth hormone, blood-clotting factors for hemophilia, and monoclonal antibodies used to treat cancers and autoimmune diseases. The hepatitis B vaccine is made by yeast cells carrying a viral gene for a surface protein, so the vaccine contains no virus at all.
• Food enzymes. Cheese needs the enzyme chymosin (rennet), which used to be taken from calves' stomachs. Since 1990, chymosin made by engineered microbes has been approved, and it is now widely used in cheesemaking.
• Detergents and industrial enzymes. Proteases and other enzymes in laundry detergents are produced by engineered microbes, often with mutations that make them work in cold water or survive bleach. (You studied industrial enzymes in the Biochemistry unit.)
• Synthetic biology. Scientists have engineered yeast with several new genes so it makes a precursor of artemisinin, an antimalarial drug normally extracted from a plant.

Agriculture: transgenic plants

To get a gene into a plant, scientists often use Agrobacterium tumefaciens, a soil bacterium that naturally inserts part of its Ti plasmid into plant DNA. Scientists remove the disease-causing genes from the plasmid, add the desired gene and a marker, and let the bacterium deliver it to plant cells growing in culture. A whole plant is then grown from a transformed cell. Another method, the gene gun, fires tiny metal particles coated with DNA into plant cells.

Examples:

• Herbicide-tolerant canola. Canola itself was bred (without genetic engineering) by Canadian scientists, including Baldur Stefansson and Keith Downey, in the 1960s and 1970s. In 1995 Canada approved its first herbicide-tolerant GM canola, which lets farmers spray a weed-killer that would otherwise kill the crop. Today most canola grown in Canada is herbicide-tolerant.
• Bt corn and cotton carry a gene from Bacillus thuringiensis for a Cry protein that is toxic to certain insect larvae (it binds receptors in their guts) but not to mammals, reducing the need to spray insecticides.
• Virus-resistant papaya helped save Hawaii's papaya industry from a plant virus in the late 1990s.
• Golden Rice carries genes from maize and a bacterium so the grain makes beta-carotene, which the body converts to vitamin A. It was designed to reduce vitamin A deficiency, a cause of childhood blindness. The Philippines approved it for planting in 2021, but in 2024 a court there ordered commercial planting stopped while legal challenges continued.
• The Arctic apple, developed in British Columbia and approved in Canada in 2015, uses RNA interference (from the eukaryotic gene-control lesson) to silence the enzyme that makes cut apples turn brown.

In Canada, any plant with a novel trait is assessed by the Canadian Food Inspection Agency (environment and livestock feed) and Health Canada (food safety) before it can be sold. In 2022 and 2023 the government updated its guidance so that gene-edited plants without any foreign DNA, whose traits could also arise through conventional breeding, are generally treated like conventionally bred plants.

Agriculture: transgenic animals

• AquAdvantage salmon carries a growth-hormone gene from Chinook salmon with a control sequence from another fish (the ocean pout), so it grows to market size faster. Health Canada approved it as food in 2016, and it was first sold in Canada in 2017. The company later raised the fish in land-based tanks in Prince Edward Island and Indiana. The fish were sterile and all-female, to reduce environmental risk. The company stopped farming the fish in late 2024 after running short of money, which shows that regulatory approval does not guarantee commercial success.
• The Enviropig, developed at the University of Guelph, made an enzyme (phytase) in its saliva that let it digest phosphorus in grain, so its manure contained less phosphorus to pollute lakes. The project ended in 2012 without the pig being approved for food.

Cloning: two different meanings

Gene cloning means making many copies of a gene, by putting it into a vector and growing the host (the last lesson) or by PCR.

Organism cloning means making an organism genetically identical to another. Dolly the sheep, born in 1996 at the Roslin Institute in Scotland, was the first mammal cloned from an adult body cell, using somatic cell nuclear transfer (SCNT). Her birth showed that the nucleus of a specialized adult cell still contains all the genes needed to make a whole animal; they had only been switched off (remember epigenetics). Cloning is still inefficient: most attempts fail.

• Reproductive cloning produces a whole animal (used for some prize livestock and to try to preserve endangered species).
• Therapeutic cloning produces embryonic cells for research or treatment, not a baby.

Gene editing with CRISPR-Cas9

Older genetic engineering mostly adds a gene. Gene editing changes a gene in its own place. Bacteria use CRISPR (clustered regularly interspaced short palindromic repeats) as an immune system: they store short pieces of virus DNA in their own genome, make RNA copies of them, and use the Cas9 enzyme to cut matching virus DNA. In 2012, Jennifer Doudna and Emmanuelle Charpentier showed that this system can be programmed to cut any chosen DNA sequence; they shared the 2020 Nobel Prize in Chemistry.

How it works:

1. Scientists design a guide RNA whose 20-base section matches the target DNA.
2. The guide RNA and Cas9 form a complex that scans DNA.
3. Cas9 only cuts where the target is right next to a PAM sequence (NGG, where N is any base, for the most common Cas9).
4. Where the guide RNA pairs with the DNA, Cas9 cuts both strands about 3 base pairs upstream of the PAM.
5. The cell repairs the break, using the systems from the DNA repair lesson:

• Non-homologous end joining often adds or deletes a few bases, causing a frameshift that knocks out the gene.
• If scientists supply a template DNA with the desired sequence and matching ends, homology-directed repair can copy it in, making a precise change.

Newer versions: base editors (2016) change one base into another without cutting both strands, and prime editors (2019) can write short new sequences; both were developed in David Liu's laboratory.

Applications (as of 2026):

• Medicine: Casgevy, the first approved CRISPR therapy, treats sickle cell disease and beta-thalassemia. A patient's blood stem cells are edited outside the body to switch on fetal hemoglobin, then returned. It was approved in the United Kingdom and United States in late 2023 and by Health Canada in 2024. In 2025, doctors in the United States treated a baby with a rare liver enzyme disorder using a base editor designed for his own mutation, the first personalized gene-editing treatment of its kind. These treatments are very expensive and complex, and long-term effects are still being studied.
• Agriculture: gene-edited crops with traits such as disease resistance or better nutrition.
• Research: knocking out genes one at a time to discover what they do.

Limits: Cas9 can sometimes cut similar sequences elsewhere (off-target effects), editing may not happen in every cell (mosaicism), and delivering editing tools into the right cells in the body is difficult.