Converting risk genes into protective genes
At PeterBio we want to make nature’s solutions to genetic diseases available through our RITDM™ technology. In nature, specific genes can exist in multiple variants, some of which can be causing diseases, but others can also be protective or leading to milder symptoms. At this moment we are focussing on chronic diseases that have a strong genetic component, such as Alzheimer’s Disease, Sickle Cell Disease, Cystic Fibrosis and Muscular Dystrophy. Also, we are applying our RITDM™ technology to modify specific genes that are underpinning next generation immune therapies for oncology.
An example of this is the involvement of the apoE gene in Alzheimer’s disease. Three major variants of this gene exist in nature: apoE2, apoE3 and apoE4. The E4 variant has been associated with increased risk for the disease, whereas the E2 variant can protect and the E3 variant is neutral. Converting the risk variant (E4) into the protective variant (E2) in the appropriate cells of the body of an at risk individual can potentially help to reduce the risk for that person to develop Alzheimer’s disease. With our RITDM™ gene-editing technology, in combination with cell therapies, we are developing novel preventative approaches.
Sickle Cell Disease
Sickle Cell Disease is caused by a point mutation in the beta globin gene. In nature some individuals who have this mutation do not develop the severe form of sickle cell disease. Studies have shown that protective mutations in other genes exist that can help to alleviate symptoms, for example by switching on another form of hemoglobin that can take over key functions. One such gene is called Bcl11A. Our RITDM™ technology can be used to replicate this compensation mechanism, reducing the impact of sickle cell disease for patients.
Duchene Muscular Dystrophy
Duchene Muscular Dystrophy can be caused by a wide variety of mutations in the Dystrophin or DMD gene. The DMD gene is one of the largest human genes. In addition to mutations that cause the most severe form of dystrophy, also mutations are known that cause a milder form of dystrophy. In most of the later cases exons (pieces of coding DNA) towards the end of the gene are missing and a shorter, but still functional form of dystrophin is formed. Our RITDM™ technology can be used to replicate this form of “exon skipping”, thereby reducing the disease severity.
Immune therapies for oncology
Recent developments show that genetics can also be used to develop new therapies for oncology. Our immune systems have the ability to identify and destroy cancer cells, but under certain circumstances this balance is tilted and cancer cells outgrow the immune surveillance. One way to give the immune cells the upper hand again is to isolate them from tumors, inactivate a gene that can switch off immune cells, multiply those immune cells and bring them back into the body. The PDCD1 gene encodes an important check-point that can result in immune cells becoming less active. We have developed a method to inactivate the PDCD1 gene on immune cells, so they can be used in next-generation immune-oncology applications.
When developing therapies for Cystic Fibrosis we are not only looking at the most prevalent mutation (deletion of codon 508) in the CTFR gene that can cause the disease. We also take into account that certain genes can act as modifiers for the severity of the symptoms.