Our project began with a strong focus on Pernicious Anaemia (PA). As our understanding and work evolved, our scope expanded to other kinds of B12 malabsorption. But PA has remained at the heart of the project, both as a central case and as a driving motivation that gave meaning to our efforts.

The autoimmune disease Pernicious Anaemia is characterised by antibodies against Intrinsic Factor (IF) or, in some cases, against the parietal cells in the stomach that produce it [2]. As shown earlier, IF plays a central role in the absorption of vitamin B12. Without sufficient IF, the body cannot absorb enough B12 to function properly. Because B12 is essential for producing red blood cells and transporting oxygen throughout the body, a prolonged deficiency leads to increasingly severe symptoms. The term ‘pernicious’ reflects the fact that, until 1926, the disease was incurable and inevitably fatal.

PA is most common in Europe, particularly in Northern European countries (2). Its global prevalence is estimated at around 0.1%, equivalent to roughly 8.1 million people. However, both the scientific literature and the experts we consulted suggest this is very likely an underestimate, as the disease remains under-researched and frequently under-diagnosed. It is often mistaken for general B12 deficiency or misdiagnosed as an entirely different condition. Some estimates place prevalence closer to 0.8%, which would amount to approximately 64.8 million people worldwide.

Note: Other conditions, like atrophic gastritis or surgical resection, can also be the reason of IF-related malabsorption and similar symptoms as PA [2].

Treatment Approaches

For diet-related deficiency: Standard B12 supplementation with tablets is usually enough.

For malabsorption-related deficiency, including PA: lifelong intramuscular injections are currently the best known treatment, because they release B12 directly into the bloodstream.

If a treatment exists, then what is the problem?

Many people with B12 malabsorption and Pernicious Anaemia endure years of unexplained symptoms, frequent misdiagnosis, and inadequate frequency of treatment, leaving a significant proportion dissatisfied with their medical care [2]. Injections, the best available treatment for B12 malabsorption and deficiency, bring emotional and practical challenges for patients because they are painful, inconvenient and not easily accessible to all. Additionally, they place a strain on the healthcare system by increasing the number of mandatory regular visits to healthcare centers, and they create significant environmental waste [5]. On top of this, B12 deficiency and Pernicious Anemia remain under-researched, poorly understood, and little known. Together, these factors create a complex situation that results in considerable, yet avoidable suffering. In light of this, the Aalto-Helsinki iGEM team decided to explore a better treatment alternative to improve accessibility, enhance patient experience, and partly relieve the strain on both the healthcare system and the environment caused by the current standard of care.

Our Solution: AbsorBuddy, a new B12-IF oral supplement

AbsorBuddy is our proposed next-generation oral vitamin B12 supplement, designed specifically for people whose absorption is impaired due to intrinsic factor (IF) deficiency or autoimmune interference, such as pernicious anemia. Current oral B12 supplements either rely on passive diffusion, which is often inadequate for IF-deficient patients, or use porcine-derived intrinsic factor, which can trigger immune responses and has not been systematically optimised for therapeutic use. Although recombinant human IF has been produced before, there has never been a comprehensive, side-by-side comparison of IF variants from multiple species to determine which is the most effective and least immunogenic. This is the knowledge gap our project is trying to address.

Unlike past iGEM and research projects that have typically focused on modifying single IF (often human) to avoid antibody binding, or have lacked robust biochemical validation of function, our approach is fundamentally different. We are expressing five distinct IF proteins, from human, porcine, bovine, rat and platypus, in the yeast Komagataella (Pichia) pastoris, an eukaryotic host that ensures proper folding and post-translational modifications, increasing the likelihood of producing proteins that are structurally and functionally equivalent to their native mammalian forms. Since the origin of species influences binding affinity, receptor interaction and antibody interference; exploring IFs from different species may identify superior candidates for enhanced B12 absorption.

To sow the first seeds of this motivation, we have designed a complete functional characterisation pipeline that balances scientific rigour with our resource constraints. Even in cases where time or equipment limitations prevent us from completing an experiment, we document detailed protocols so that future teams can build on our work, ensuring a lasting contribution to the iGEM community.