Reflecting on Project Development

We believe that a crucial part of our project is to approach it with integrity by openly acknowledging its limitations and discussing the steps we took to address them. When 2025 began, our team envisioned a project that looked quite different from what UNIglobin would eventually become.

At the beginning of our cycle, as part of our recruitment process and brainstorming stage, we hosted the Idea Bowl. This three week long process was a chance for our team members to split up into mini groups, identify global issues and brainstorm possible solutions using synthetic biology. The Idea Bowl concluded with groups presenting their proposed project to “judges” – our PI and bioengineering faculty members, Dr. Benjamin Bartelle and Dr. Christopher Plaiser, as well as multiple past iGEM members. The presentation day mimicked an iGEM judging session with groups having a slideshow presentation, time limit, and questions/feedback from our “judges”.

Advisor feedback and team discussion narrowed our project idea to focus on some type of blood conversion. The initial paper that inspired this idea identified an enzymatic pathway from the human gut microbiome that cleaves A antigens and demonstrated successful conversion of A type blood to O type blood [1]. Our initial iGEM proposal was to utilize directed evolution to improve the cleavage efficiency of this enzyme. However, through further deliberation amongst ourselves and advisors, we realized this project area was already well-developed as the work from the 2019 of had since progressed into a company. Thus, we decided to explore a different direction where we could make a unique contribution.

To add a new aspect to our project, we decided to explore applications in xenotransplantations and xenotransfusions. Xenotransplantation research has recently grown rapidly [2, 3], providing many opportunities for innovation. One of the major challenges in this field is hyperacute rejection, which is triggered by the xenoantigen α-galactose present on porcine red blood cells. Current approaches to target this antigen include knocking out the gene that produces the α-galactose epitope. However, using synthetic biology, we wanted to use the α-galactosidase enzyme to cleave off the antigen. At this stage, we still envisioned a project focused primarily on technical enzyme optimization within the lab, along with proof-of-concept demonstrating the full conversion of porcine blood to compatible human blood.

After discussing and gaining feedback with experts in the fields of both xenotransplantation and bioethics, we pivoted our project yet again. Through reviewing literature on enzymatically converted group O Red Blood Cells (ECORBC) and past iGEM team’s work, we found two key pieces of information that would inspire us to take on our current project, UNIglobin. First, TAS-Taipei’s 2021 team developed a project targeting A and B antigens, which helped us guide our thinking as we developed UNIglobin. Second, a 2024 paper published in Nature Microbiology documenting and characterizing the activity of enzymes from the gut symbiont Akkermansia Muciniphilia AmGH36A, AmGH35A, AmGH95B, AmGH20A, and AmGH110A. The authors proposed that combining these five AmGH enzymes enables cleavage of not only the A and B antigens but also their extended epitopes [4]. We saw an opportunity to incorporate these enzymes into our work as a way to build upon and extend previous work done in iGEM, while still staying connected to our original idea at the beginning of the cycle.

Incorporating Diverse Perspectives

In order for our project to be implemented responsibly, we made sure to not only focus on positive outcomes but to also take into consideration the potential negative impacts that may arise and address them. We did this via stakeholder meetings and a survey gauging public perception, which gave opportunities for professional and ethical feedback.

Bioethics

• Description: Dr. Johnson, a bioethics professor at SUNY Upstate Medical University, focuses on animal research ethics and xenotransplantations. In the beginning of the cycle, while we considered a xenotransfusion focused project, we noticed several ethical concerns relating to inclusivity, public perception, and animal welfare. We reached out to her for guidance on how to thoughtfully address these concerns within our project.
• Summary: Thanks to Dr. Johnson, we were quickly prompted to think about technical limitations of our project such as the potential for zoonosis diseases, and ethical limitations such as biosurveillance of xenotransfusion patients, and religions objections to that can’t accept blood transfusions or porcine products such as Jehovah's Witnesses, Judaism, and Islam.
• Reflection: To address concerns for zoonotic diseases, we went back to the literature to identify any potential pathogens present on porcine blood. From which, we’ve identified porcine cytomegalovirus (PCMV), porcine endogenous retrovirus (PERV), porcine lymphotropic herpesvirus PLHV, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. We then started to research whether biological assays to detect these pathogens exist or if we would need to develop them. To address religious concerns, we interviewed a Jehovah’s Witness group on campus, which you can find below.

Jehovah’s Witness Group

• Description: Inspired by suggestions from previous professors to engage with religious groups that have blood transfusion limitations, we interviewed a Jehovah’s Witness group on campus. We wanted to better understand their views on blood transfusions and where the beliefs regarding it stemmed from, in hopes we can implement their input/concerns into our project.
• Summary: The group explained the biblical history of abstaining from blood as in their religion, blood is a holy gift from God and therefore should not be consumed or tampered with. They also told us alternative methods used in place of blood transfusion such as using non-blood fluids to replace volume. When asked about the use of blood transfusion in emergencies or the use of artificial blood, the group agreed that it would be up to the individual's “conscious choice”. They also shared how they have a hospital liaison committee to help advise healthcare professionals who treat Jehovah’s Witness patients.
• Reflection: We thought about ways that we could implement their practices into our project, such as developing ways to produce artificial blood. Ultimately, we decided this would not be feasible for us in this cycle due to our limited resources. Also, their emphasis on an individual’s right to “conscious choice” furthered our concerns to ensure informed consent. Because we envision our kit to be used in emergency medical situations we hope that everyone and anyone can safely use our product regardless of background.

• Description: Dr. Hurst is Director of Medical Professionalism, Ethics, & Humanities at Rowan-Virtua School of Osteopathic Medicine with research interests in xenotransplantations. He has published on the importance of public engagement with xenotransplantation. We reached out to Dr. Hurst to discuss how to navigate public perception of our project and how to incorporate these perspectives into our work, given our initial interest in xeno-related procedures.
• Summary: Dr. Hurst discussed his xenotransplantation survey results, showing us how generally people have a more positive public perception of xenotransplantation compared to xenotransfusion. Due to his survey being completed by a generally older population, he suggested we make a survey specifically for ASU students. This would give us the opportunity to see age-related changes and trends.
• Reflection: We made a public opinion survey, utilizing tips that Dr. Hurst provided, such as distributing the survey to other college students and using a Likert scale for measurement. We also started to explore other avenues our project could take, as he highlighted an important point we hadn’t considered before: Organs are more limited than blood, which may influence how the public prioritizes xenotransplantation. This further emphasized a lack of need for our project, prompting a shift of our focus away from xenotransfusions and towards human blood conversion to O blood.

• Description: Dr. Padilla is an epidemiology professor and Vice-chair of the IRB at University of Alabama Birmingham. She has research interests in xenotransplanatations and has published multiple reviews and surveys regarding public attitudes towards xenotransplantations. Through our meeting with Dr. Padilla, we hoped to ask her advice regarding our wet lab workflow and thoughts about our project idea and feasibility.
• Summary: Dr. Padilla offered a number of ethical questions that we could ask throughout our research: What is the level of preformed antibodies? Will immunosuppressive therapy be needed? What is the risk benefit analysis? Because of the possible unknown pathogens present in pig’s blood, there poses greater risks in xenotransfusion than in enzymatically converted human blood transfusion. Overall, this meeting emphasized that while enzyme cleavage may be successful, there may be a large gap between in vivo and clinical trials that needs to be addressed. In the context of our project, this could mean that enzymatic activity and efficiency is even more crucial to assess, since we need to achieve complete cleavage of the antigen. But even with that in mind, there is never a 100% certainty that there is no risk in xenotransfusion.
• Reflection: We further considered the risk-benefit analysis of our project and realized the xenotransfusion project may not be as feasible as we thought. A significantly large gap between in vivo and clinical trials needs to be addressed. The culmination of these past few bioethics meetings was the turning point to pivot our project away from xenotransfusions and towards human blood compatibility instead.

Laura Hwa (TAS-Taipei)

• Description: Laura Hwa is a current senior undergraduate at Princeton University studying Computer Science. We reached out to her due to her Human Practices involvement on the 2021 TAS-Taipai iGEM Team (UniversO). We hoped to learn more about their thought process regarding Human Practices work and general advice on having a successful project.
• Summary: We asked Laura about how the TAS_Taipei team identified and contacted their stakeholders. She gave us contact information about the bloodbanks they talked to and explained the reasoning behind contacting each one. We were also curious about additional activities the 2021 team wished to pursue if they had more time in the cycle. Her response informed us about doing more research regarding blood supply and where their product would fit within the blood donation supply chain. She also suggested we do more research into current state of the art practices in synthetic/animal blood to compare what our product would bring to the current field.
• Reflection: The main theme of Laura’s suggestions was to make sure we establish a need for our product. We identified that our product would be ideally used in emergency cases (i.e., natural disasters or war zones) where blood supply is depleted, or in blood deserts. Her suggestions also prompted us to contact AzCHER (AZ Coalition for Healthcare Emergency Response), a state-wide organization that is committed to preparing healthcare facilities in Arizona for emergencies, as they conducted a “Medical Supply Chain Integrity Assessment” in 2021 that included blood supply.

Wet lab/Dry lab

• Description: Jeffery Wolz is the faculty director of the medical laboratory science program at ASU’s Downtown Phoenix Campus. We reached out to him due to his specialty in immunohematology. He often teaches classes involving laboratory techniques that we are interested in, such as crossmatch hemagglutination.
• Summary: During our meeting, we asked a number of questions regarding our assay methods and hardware design. For our crossmatch hemagglutination assay, Wolz helped explain and differentiate the uses of each method, including slide agglutination, test tubes, or gel card typing. For hardware, we asked about portable methods of RBC separation from whole blood, which we were informed would not be a simple process. He also pointed out that in later stages, regulation of our overall device could be a hurdle.
• Reflection: We reviewed Professor Wolz’s protocols in depth and identified the methods that would best fit our project needs the most. Based on his protocols and advice, we adapted the hemagglutination protocol by implementing the method of test tube agglutination. While this approach is less sensitive than the microtyping gel card method, test tube agglutination using recipient serum eliminates the need for antibody serum and specialized equipment for gel cards. We also considered other methods of RBC separation and centrifugation viability in operative fields, leading to us adopting our SCOBY + PTFE filter method.

Enoch Toh (TAS-Taipei)

• Description: Enoch Toh is a current senior undergraduate at Johns Hopkins University studying Computer Science and Molecular Biology. We reached out to him due to his leadership of the 2021 TAS-Taipei iGEM Team (UniversO) wet lab team, who similarly targeted human blood antigens with enzymes with the goal of manufacturing “universal” O blood (ABO-type universal). We hoped to learn about their assays, hardware, Human Practices, and gain some advice on leading a successful project.
• Summary: Enoch described his team’s difficulties in finding good models for testing, resulting in them using porcine RBCs. He advised us that if we have the opportunity to use human RBCs, we should go for it. Furthermore, for his team’s colorimetric assay, they bought commercially available substrates, listing alpha gal as a widely used candidate. Regarding hardware, we asked about the advantages of immobilizing enzymes on beads, and Enoch advised that they made this design choice so that enzymes don’t have to be separated out of the blood in a subsequent step. He also described that he wished his team had focused more on developing a physical prototype of the hardware, which he stated was where the most novelty and impact could be found from. For Human Practices, he advised that the best way to promote/collect responses for a public survey was through social media. He also relayed the importance of thinking about the justification and certain safety considerations, why this approach might be more beneficial than artificial RBCs, and how to ensure/quantify reaction completeness.
• Reflection: We looked into how to obtain approval to start human and porcine blood experiments. Regarding human blood experimentation, we found it infeasible to obtain IRB approval for this given project. However, we were able to turn in the iGEM Check-in form and obtain approval for porcine blood experimentation using human serum, which we used for our hemagglutination assays. We also researched where to find commercial substrates for our enzymes to replicate their colorimetric assays. Finally, we started to work on developing schematics for our hardware design so that we could have a functional prototype to start testing with.

• Description: Dr. Samantha Phou is a pathologist who specializes in anatomic and clinical pathology and blood bank and transfusion medicine at Phoenix Children’s Hospital. We reached out to her because of her expertise in transfusion medicine. We hoped to further our understanding of the blood transfusion process and ensure our enzymatic conversion kit takes the proper safety steps into consideration.
• Summary: We asked a series of questions regarding the process of transfusions and safety steps that are commonly taken. One concern we had was what steps usually occur after transfusions and how blood testing/monitoring in the field can occur. Dr. Phou described that after transfusion, monitoring of antigen, hemoglobin, hematocrit, and bilirubin levels typically occur in clinical labs. These measurements tell you if a patient is hemolyzing, and the solution to this would be transfusing blood that doesn’t cause an immune reaction, which might be an issue in our kit given its premise being a lack of supply of transfusable blood. We also asked about the advantages and disadvantages of administering whole blood versus the individual components in the field, as administering plasma, erythrocytes, and platelets may have advantages when someone is losing a lot of blood. Dr. Phou described that whole blood is only used with type O donors who have low titers of anti-A and anti-B. For our application plasma would not be transfusable, but platelets may be alright. We also asked about the levels of how low residual a/b unit levels that are must be to be considered safe. Dr. Phou described that it takes very little ABO incompatible blood to cause a hemolytic reaction (<15 mL). She also described that A1 blood types typically have more A antigen than A2 or A3, and these levels play a major role in the antigenicity of A1 blood compared to other A subtypes. Within our kit hemolysis after transfusion is a huge concern, and therefore it is extremely important to ensure complete enzymatic cleavage.
• Reflection: Our next steps are to adapt parts of the hardware to take these safety precautions into account. We will ensure plasma and leukocyte depletion with our biological reduction strategy through experimentation, since Dr. Phou established this importance in our kit in particular.

Blood Conversion Public Opinion Survey

• Description: Inspired by the feedback of Dr. Daniel Hurst, we designed a public opinion survey to distribute to the ASU population. Our goals for surveying were:
  1. Understand the population’s knowledge regarding blood transfusion and genetic modifications.
  2. Learn about the public's opinion regarding ours and others blood transfusion technology.
  3. Gauge the public’s opinion on alternative blood transfusion techniques including artificial blood and xenotransfusions.
  4. Learn about the public’s opinion regarding use of genetic modifications in healthcare and medicine.
• Results: We received 38 responses. The demographics of the surveyed population are described below.




• Reflection: Through this survey, we were able to engage many ASU students. We learned that the surveyed population was generally knowledgeable regarding blood transfusions. A majority of participants self-reported being familiar with both blood transfusions and genetically modified organisms (GMOs). Regarding voluntary blood donation trends, we learned that although only 13% of participants reported donating blood in the past year, an overwhelming majority (71%) stated they are more than willing to donate blood in the next year. Furthermore, when asked about their willingness to accept genetically modified blood, participants felt generally neutral (45%) and comfortable (37%) with the idea. However, their acceptance significantly dropped when asked about receiving xenotransfusions from chimpanzees, pigs, and dogs, further emphasizing our project’s appeal over alternatives. Additionally, since our survey population was majority college-aged students, we believe that these generations may be more accepting of such biotechnological advancements. This also raised a concern of potential misuse of not only our product but products emerging from biotechnology as a whole. If the public is overly accepting or indifferent towards such new biotechnological advancements, they may be more susceptible to misuse of potentially harmful products. This concern is further addressed during our high school outreach events. Lastly, in the future we want to look into ways to better distribute our survey to the public. This year, we were limited to sending in the iGEM Global Slack and sharing with our classmates.

Exploring Context Beyond the Lab

Emergency Blood Shortages vs Blood Inaccessibility

During our exploration of the possible applications for our project, we found that our blood conversion kit (the UNIGlobin Enzymatic Blood Conversion Kit) has the potential to address both emergency blood shortages and blood inaccessibility. While they may seem synonymous at first, our review showed that they arise from different causes and can, at times, intersect in practice.

Emergency blood shortages are disruptions to existing blood supply chains that can be caused by a number of events, such as global pandemics (e.g. COVID-19 in 2021), the occurrence of natural disasters that result in mass casualties, or even seasonal trends that result in a decline of donor populations [5]. On the other hand, blood inaccessibility is characterized by the systematic lack of adequate resources and medical infrastructure that would ensure doctors and patients in a region have safe access to blood. In areas facing this burden, blood supply chains have pervasive vulnerabilities in all facets– from donor availability, to blood processing, and to blood delivery. Overall, both scenarios risk blood unavailability (i.e., the unmet need of blood), as depicted in Figure 1.

In the sections below, we explore the strategies that interdisciplinary experts have identified are important to address the causes for blood unavailability in a feasible, context-dependent manner. Then, we outline how we incorporated these methods into our wet lab, hardware, and Human Practices work, as well as the limitations of our approach.

Improving Blood Accessibility: Understanding Global Blood Deserts

According to the most recent WHO data report on “Blood Safety and Availability”, 118.5 million blood donations are collected globally each year, but nearly 40% come from high-income countries that make up just 16% of the global population [7]. Meanwhile, low and middle income countries (LMICs) face an unmet need of more than 100 million blood units. Every South-Asian, Sub-Saharan Africa, and Oceanian country experiences persistent shortages [8]. Compared to HICs, LMICs typically experience a need for blood that is multiples higher than blood supply, as shown in Figure 2. However, low-resource settings in high income countries, like rural areas and underserved communities, can also experience recurring shortages.

A term for these areas characterized by blood inaccessibility was clearly defined by an interdisciplinary panel of doctors, patient advocates, and international health policy experts in 2024, as shown below:

The Blood DESERT Coalition is an organization dedicated to developing and advocating for strategies that support the education and research necessary to eliminate blood deserts around the world. The resources they provide aim to close the gap in blood supply between high-income (HI) countries and low-to-middle income (LMIC) countries.

It is important to acknowledge that in the long-term, establishment of robust and efficient blood banking systems will be most effective in providing those in blood deserts with the sufficient healthcare they deserve. However, because blood banking is expensive and logistically challenging, the Blood DESERT Coalition has identifiedb 3 innovative strategies to produce immediate effects and provide more blood in the short-term, as shown below [6]:

Of these 3 strategies, our blood conversion kit/technology is primarily framed around #1: Walking Blood Banks (WBBs). WBBs rely on a pool of close-by donors that are pre-screened for pathogens and blood type. In case of emergency, these prospective donors can undergo Rapid Diagnostic Testing (RDT) for expedited screening. Operators in the field are then able to quickly assess compatibility, at which point whole blood can be immediately collected and transfused [2]. Historically, walking blood banks have been utilized in military and other similar disaster settings [8].

A drawback to consider with walking blood banks is that reliance on existing healthy and compatible donors may be limited in areas with smaller populations. Secondly, unprocessed whole blood transfusion can be an issue, since the donor’s blood could contain antibodies against the recipient’s blood. For example, while O type blood is typically transfusible to the A, B, and AB types, its plasma contains anti-A and anti-B antibodies, so it cannot be transfused in whole blood form. Unless technology for separating plasma from red blood cells is available, donor type would have to be identical to the recipient’s.

In the case that a compatible donor is unavailable, our kit provides a supplementive route for providing compatible blood. An important trade-off to consider is that if a donor has unknown health risks, screening for donor risk and Transfusion-Transmissible Infections (TTI) cannot be expedited via RDT, so diagnostic tests must be more rigorous and potentially more expensive. Thus, we attempted to reduce costs for all possible components, such as through our SCOBY filter for leukocyte reduction/plasma filtration and lectin-based Miniaturized Electronic Antigen Biosensor (MEAB).

Over-reliance on a biotechnological solution could unintentionally reduce investment in donor recruitment or infrastructure. Thus, we aim for our kit to supplement existing strategies and integrate into the global blood supply, rather than replace safe blood banking practices. As shown in Figure 3, our product can be utilized in any scenario where banked, compatible blood is in no way available.

Addressing Emergency Blood Shortages: Exploring Blood Shortages in the United States and Arizona

To better understand how and why emergency blood shortages affect our local community, we reviewed the “Medical Supply Chain Integrity Assessment” written in 2022 by AzCHER (Arizona Coalition for Healthcare Emergency Response), a nonprofit organization dedicated to emergency healthcare readiness in Arizona. This report allowed us to identify the events that would result in a medium to high likelihood of disrupting Arizona’s blood supply chain, such as:

• Increased Demand
• Decreased Supply
• Uncertainty of Demand and Supply
• Delivery Delays
• Increased costs (Products, Labor)

While our conversion kit could apply to situations of increased demand, decreased supply, and delivery delays, it may be limited in scenarios of increased costs. This is because implementing our kit would require extensive efforts to ensure that it is ready to deploy in healthcare fields. Qualifying new products, or proposing them for introduction to healthcare delivery systems, can be an expensive process due to the rigorous questions involved. For example, we would have to ensure that our product not only does what it says it does, but also has consistently reliable outcomes and clearly outlined steps for specialized training [11]. The assessment also shares that the key challenge for those who create these new products is to clearly document information within the “product catalog”. Although our toolkit is in the very early stages of development, we have outlined a timeline of future steps needed to responsibly optimize our workflow and develop it into a marketable product.

Blood Drive

While our technical project explores one potential path to providing more blood for transfusions, we also recognize the importance of strengthening the broader ecosystem of blood donation.

During the first full week of classes, we hosted a blood drive on-campus. We hosted with the help of Vitalant, a non-profit organization that provides hundreds of blood and other biological units to healthcare facilities throughout Arizona and the United States. Our drive resulted in 23 blood products being collected, providing care for 69 patients.

As the main theme of our project is making safe blood more accessible, we wanted to provide an opportunity to directly provide more blood products to our local community. Beyond helping the local blood supply network, we also wanted to take the opportunity to teach people about the importance of blood and better understand the blood donation process.

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Initially, those of us tabling at the blood drive had expected that the turnout of spontaneous donors would be low. However, while encouraging passerby students to donate, many had expressed interest and signed up to donate in the moment! There were also many students who expressed interest but could not donate because they were on their way to class. Overall, we realized that people are generally very willing to donate blood, but barriers such as a lack of proper education/promotion of blood drives or a lack of time for the donor themselves. These findings are also supported by our public opinion survey, where the most common reasons for not donating are not having the time to go donate and the fear of negative side effects. For the latter reason, we believe that if we continue to educate the public about the blood donation process and the importance of blood transfusions, we can open up people's views to consider the outweighing positive side effects.

Applications in Xenotransplantation and Xenotransfusion

As mentioned above, our initial iGEM project was centered around xeno-related procedures and improving compatibility between porcine blood and human blood. Current approaches to improve compatibility include genetic knockouts of α-galactose epitope forming genes. However, we envision the UNIglobin blood conversion kit to have applications for porcine blood as well. This is because AmGH110A (B1), the enzyme we use to cleave the B antigen, is an α-galactosidase, meaning it can also be used to cleave the α-galactose group on porcine blood.

Enzymatic conversion of the immunogenic a-gal epitope may serve as an alternative to genetic engineering. However, aside from the concerns of enzyme efficiency and complete antigen cleavage in our wet lab work, there remain several technical and ethical issues surrounding the use of donor pigs in xenotransplantations and xenotransfusion.

In 2001, The United States Food & Drug Administration (FDA) developed a Public Health and Safety Guideline on Infectious Disease Issues in Xenotransplantation. Due to rising interest in xenotransplantation research, this guideline is extensively reviewed, with its latest revision in 2022. The FDA lists 3 primary concerns:

1. “The potential risk of transmission of infectious agents from source animals to patients, their close contacts, and the general public”
2. “The complexities of informed consent”
3. "Animal welfare issues” "

While these concerns are primarily involved in later stages of research and implementation, we acknowledge that it is important to integrate with all stages. Thus, we met with professors involved in animal research ethics, surveying public perception, and xenotransplantation research.

References

[1] Rahfeld, P., Sim, L., Moon, H., Constantinescu, I., Morgan-Lang, C., Hallam, S. J., Kizhakkedathu, J. N., & Withers, S. G. (2019). An enzymatic pathway in the human gut microbiome that converts A to universal O type blood. Nature microbiology, 4(9), 1475–1485. https://doi.org/10.1038/s41564-019-0469-7

[2] Groth, Carl G.. The potential advantages of transplanting organs from pig to man: A transplant Surgeon's view. Indian Journal of Urology 23(3):p 305-309, Jul–Sep 2007. | DOI: 10.4103/0970-1591.33729

[3] Lee, S.A., Lafargue, MC., Williams, W.W. et al. Physiologic Homeostasis in a Living Human after Pig Kidney Xenotransplantation. Nat Commun 16, 8453 (2025). https://doi.org/10.1038/s41467-025-63153-3

[4] Jensen, M., Stenfelt, L., Ricci Hagman, J., Pichler, M. J., Weikum, J., Nielsen, T. S., Hult, A., Morth, J. P., Olsson, M. L., & Abou Hachem, M. (2024). Akkermansia muciniphila exoglycosidases target extended blood group antigens to generate ABO-universal blood. Nature microbiology, 9(5), 1176–1188. https://doi.org/10.1038/s41564-024-01663-4

[5] N. N. Saillant et al., “The National Blood Shortage—An Impetus for Change,” Ann. Surg., vol. 275, no. 4, p. 641, Apr. 2022, doi: 10.1097/SLA.0000000000005393.

[6] N. P. Raykar et al., “Innovative blood transfusion strategies to address global blood deserts: a consensus statement from the Blood Delivery via Emerging Strategies for Emergency Remote Transfusion (Blood DESERT) Coalition,” Lancet Glob. Health, vol. 12, no. 3, pp. e522–e529, Mar. 2024, doi: 10.1016/S2214-109X(23)00564-8.

[7] Global Status Report on Blood Safety and Availability 2021, 1st ed. Geneva: World Health Organization, 2022.

[8] Brigmon, E. P., Cirone, J., Harrell, K., Greebon, L., Ngamsuntikul, S., Mendoza, A., Epley, E., Eastridge, B., Nicholson, S., & Jenkins, D. H. (2024). Walking blood bank: A plan to ensure self-sufficiency in an era of blood shortage. Trauma Surgery & Acute Care Open, 9(Suppl 1), e001151. https://doi.org/10.1136/tsaco-2023-001151

[9] N. P. Raykar et al., “Assessing the global burden of hemorrhage: The global blood supply, deficits, and potential solutions,” SAGE Open Med., vol. 9, p. 20503121211054995, Nov. 2021, doi: 10.1177/20503121211054995.

[10]Nicholas Roberts, Spencer James, Meghan Delaney, Christina Fitzmaurice. The global need and availability of blood products: a modelling study. The Lancet Haematology. https://doi.org/10.1016/S2352-3026(19)30200-5.

[11] Introduction to Writing Emergency Plans. (2022, August 18). AzCHER. https://azcher.org/coalition-plans-and-documents-2/medical-supply-chain-integrity-assessment/