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Medicine

Synthetic Antibodies Enable Organ Regeneration and Repair

Researchers from the Leslie Dan Faculty of Pharmacy and the Donnelly Centre for Cellular and Biomolecular Research worked in close collaboration on a study related to synthetic antibodies.

The study proved fruitful as it provided crucial insight into the importance of synthetic antibodies and its wide applications.

Sachdev Sidhu, a professor at the Donnelly Centre for Cellular and Biomolecular Research, was the lead researcher on the study. He studied the binding effect that antibodies exhibit. Stephane Angers was the other lead on the study. He is an Associate Dean of Research in the Leslie Dan Faculty of Pharmacy.

How can synthetic antibodies help?

Body’s immune response forms antibodies with the arrival of antigen. Synthetic antibodies are capable of enhancing the regenerative abilities of the body. Antibodies can bind and dictate the functioning of certain proteins and cells hence they can be useful in numerous ways.

The formation of synthetic antibodies in the laboratories involves extraction of the genome and assistance of protein engineering technologies.
Researchers from the Leslie Dan Faculty of Pharmacy and the Donnelly Centre for Cellular and Biomolecular Research have recently published a new study in the journal eLife. It highlighted that one of the vital applications of these synthetic antibodies is its ability to stimulate the process of regeneration in the body tissues.
The efforts of Toronto Recombinant Antibody Centre, along with the Donnelly Centre enabled the production of a wide variety of synthetic antibodies. Several types of research and discoveries made use of these antibodies.

The newly launched therapeutics Toronto startup, AntlerA enables the antibodies application as regenerative medicine.

Sidhu, who co-founded AntlerA, was particularly excited about the use of synthetic antibodies as regenerative medicine. He was hopeful that in collaboration with the facilities in Toronto and the stem cell research regenerative medicines could be mass-produced.

Countless lives could be saved if the project is executed.

Another application of synthetic antibodies is to mimic the key growth factors, proteins called Wnt. These proteins cause stem-cell activation thus promotes the repair of injured tissues in adults. However, the hyperactivity of Wnt proteins may lead to cancer.

Wnt stimulates the stem cells to form tissues in the embryo.

The race to purify the Wnt proteins has been ongoing for years. Despite the efforts, there has been no meaningful progress. Wnt proteins not only require purification but much more. These proteins need a particular way of engineering for the preparation of medicines.

Currently, the complicated chemistry of Wnt restricts its application as a drug-molecules. The isolation of Wnt is difficult due to its binding with the lipid or fat molecules. Moreover, the lipid part of its configuration hinders its dissolution with water thus it is impossible to inject it.

These circumstances lead to the formation of antibodies which has characteristics like those of Wnt. These water-soluble antibodies are capable of binding and activating Frizzled and LRP5/6 the two classes of Wnt receptors, thus can be effectively used as medicine.

Can FLAgs be the future of regenerative medicine?

The name FLAgswas coined for the antibodies as they had the Frizzled and LRP5/6 Agonists. The antibodies can be designed to replicate any one of the hundreds of possible Wnt-receptor combinations. Humans have 19 different Wnt proteins that can activate 10 Frizzled and eight co-receptors including LRP5/6.

To generate FLAgs, Yuyong Tao, a postdoctoral fellow in Sidhu’s lab, came up with a new molecular configuration that does not exist in nature hence the term synthetic antibodies.

Natural antibodies have two binding sites, allowing them to bind to two targets. In addition to the two FLAgs have two more, which means that a single molecule can recognize multiple receptors at the same time. Also, it will mimic how Wnt proteins act in the body.

Stimulating tissue regeneration and repair

When added to cell culture, FLAgs were able to substitute for Wnt proteins which is absolutely necessary for the culture medium. They stimulated the formation of stem cell-derived intestinal organoids, three-dimensional balls of tissue that resemble the small intestine.

The only bottleneck in carrying out this in the past was the volatile nature and complex composition of the Wnt proteins. But now with modern research, use of FLAgs have made easy to activate the stem cells. Additionally, these can be mass-produced.

When injected into mice, the FLAgs were able to activate the gut stem cells, showing that the antibodies are stable and functional inside the body.

The findings raise hope that FLAgs in future could prove to be helpful as a treatment for irritable bowel disease and other ailments. It can help regenerate the intestinal lining when it is damaged. There is no definitive remedy available for the irritable bowel syndrome currently.

Other FLAg variants show promising results in lung, liver and bone regeneration. It also shows potential for treating eye disease.

AntlerA has already attracted investment to develop FLAgs into cutting edge therapeutics. He is actively working on treatments for vision loss and bowel diseases.

The startup’s name came into being because of FLAgs’ geometrical shape which resembles the antlers of deer and moose. These are the fastest regenerating organs in animals. If AntlerA is successful in mass-producing drugs using FLAgs millions of people across the globe would benefit from this research.

Emma Colleen

Emma’s professional life has been mostly in hospital management, while studying international business in college. Of course, she now covers topics for us in health.

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