Scientists at Belgorod National Research University have pioneered a method to genetically modify rabbits by inactivating the CSN2 gene, enabling them to produce milk devoid of the primary allergen responsible for dairy allergies.
Currently, approximately one in 50 children and one in 100 adults suffer from allergies to milk and dairy products. Research indicates that β-casomorphins, a group of opioid peptides released from β-casein in milk, may be to blame. These peptides can impair the body's immune response, making it less resistant to infections and foreign organisms, and are also implicated in the development of Type 2 diabetes. Interestingly, other forms of casein either do not trigger allergies or are significantly less common allergens.
This innovative project is a collaboration between BelSU, Belgorod State Agrarian University named after Vasily Gorin, and the VLADMIVA holding company, aiming to produce rabbits that secrete milk without β-casein. This hypoallergenic milk could serve as a raw material for dairy products in the food, pharmaceutical, and chemical industries.
The breakthrough in creating these rabbits was achieved through targeted genome editing, specifically the knockout of the CSN2 (β-cas) gene. The methodology was developed by researchers at the BelSU Joint Centre for Genetic Technologies, led by director Alexey Deikin.
Genetic engineering procedures involving reproductive material were conducted at the BelSU Experimental Biological Clinic by young scientists from the BelSU Research Institute of Pharmacology of Living Systems, under the guidance of Vladimir Pokrovsky, assistant professor of Pharmacology and Clinical Pharmacology, and junior research fellow at the Laboratory of Gene Editing in Veterinary Medicine and Biomedicine. The embryo transplantation, along with postoperative and postpartum care for the resulting offspring, was managed at Belgorod State Agrarian University. The coordination of this tripartite agro-scientific project was facilitated by VLADMIVA, the industrial partner of Belgorod State University.
To implement this method, a normal zygote – a fertilized egg – is microinjected with a genetic construct containing a mixture of subgenomic mRNA and the CRISPR/Cas9 enzyme. The surviving embryos are then implanted into the wombs of standard rabbits. This process has yielded 640 live zygotes, which were transplanted into 32 recipient does. Out of the 17 kittens born from these kindlings, genetic testing confirmed the successful knockout of the CSN2 gene in four rabbits, indicating an efficiency rate of 23.5%.
Vladimir Pokrovsky expressed optimism about the potential of genome editing technologies to create rabbits with enhanced characteristics that are more resilient to diseases and environmental stressors.
"These rabbits could be instrumental in studying genetic diseases, paving the way for new treatment and prevention methods. They may also produce antibodies and other biologically active substances beneficial for medicine, significantly accelerating the development of new drugs and vaccines," he stated.
The anticipated results of this research hold great promise for expediting drug and vaccine development, which is crucial in combating various diseases.
The unique method for producing genetically modified rabbits with a CSN2 gene knockout is protected by a Russian patent. VLADMIVA has already begun implementing this patented technique for the industrial production of hypoallergenic rabbit milk.
Valentin Chuev, the CEO of VLADMIVA, announced that an effective and safe process for milking rabbits has been successfully established on farms created in collaboration with Belgorod State Agrarian University. The company is already utilizing both dry and frozen rabbit milk in cosmetology, where it serves as an effective skincare product.
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