Our Technology
A proprietary fusion enzyme platform built on over 25 years of pioneering gene therapy and ERT research by Dr. Baodong Sun.
The Science Behind Spell
Spell Therapeutics is founded on the inventions of Dr. Baodong Sun, Ph.D., Associate Professor and Principal Investigator in the Division of Medical Genetics at Duke University School of Medicine, and a member of the Y.T. and Alice Chen Pediatric Genetics and Genomics Research Center.
Over a career spanning more than 25 years at Duke, Dr. Sun has been at the forefront of developing translatable therapies for rare genetic diseases, with a deep focus on lysosomal storage diseases and glycogen storage disorders. His laboratory has produced a prolific body of peer-reviewed research that has fundamentally advanced the field.
Dr. Sun's work sits at the critical intersection of two therapeutic modalities — enzyme replacement therapy and adeno-associated virus (AAV) gene therapy — giving Spell Therapeutics a unique dual-platform advantage that few competitors can match.
Pioneered the AAV liver-targeted gene therapy strategy in which the liver acts as a depot to produce and secrete therapeutic enzyme into blood circulation — a potential one-time curative approach.
Demonstrated that AAV vector administration with a liver-specific promoter can prevent anti-drug antibody formation during enzyme replacement therapy, significantly enhancing ERT efficacy.
Published key research showing that the poor ERT response in skeletal muscle is caused by low abundance of the cation-independent mannose-6-phosphate receptor (CI-MPR) — the scientific foundation for Spell's IGF2 bypass approach.
Developed enhanced AAV vectors encoding chimeric, highly secreted acid alpha-glucosidase that increase receptor-mediated uptake in striated muscle tissue.
Recently received an NIH R01 grant (~$2.7 million over 5 years) to develop and identify a lead clinical-candidate AAV vector for Pompe disease.
Research Breadth
Dr. Sun's laboratory has published extensively on therapeutic approaches for multiple glycogen storage and lysosomal storage diseases, building a comprehensive understanding of enzyme biology that directly informs Spell's platform design.
Decades of research on AAV-mediated gene therapy and enhanced ERT for Pompe disease, including liver-targeted and muscle-targeted approaches. Duke faculty led the clinical development of the first FDA-approved ERT for Pompe (Myozyme/Lumizyme).
Developed novel AAV gene therapy for glycogen storage disease type IIIa using bacterial glycogen debranching enzyme, demonstrating the lab's ability to innovate across disease boundaries.
Research spanning Fabry disease, Mucopolysaccharidoses, and other LSDs — providing the scientific foundation for Spell's broadly applicable fusion enzyme platform.
The Breakthrough
Dr. Sun's research revealed a critical problem: current ERTs depend on the mannose-6-phosphate receptor (M6PR) to deliver therapeutic enzymes into cells, but this receptor is scarce in several critical tissues — particularly skeletal muscle, kidney, heart valves, and lung.
His invention solves this by engineering an IGF2 (insulin-like growth factor 2) tag fused to the therapeutic enzyme. This tag binds to a different, far more abundant receptor pathway, dramatically increasing enzyme uptake in exactly the tissues where current ERTs fail.
Platform Advantages
Significantly improves targeting to skeletal muscle, lung, heart valve, and kidney — the tissues where current ERTs fail.
Lower effective doses mean improved safety profiles and fewer side effects for patients.
Dramatically decreases recombinant enzyme manufacturing expense, improving margins and patient access.
Platform can be applied to most lysosomal storage diseases, expanding therapeutic options across the entire LSD space.
Compatible with both classical ERT (current $10B+ market) and AAV-mediated in vivo ERT (future gene therapy market).
Exclusive in-license of IGF2 patents from Duke University. Global commercial rights fully owned by Spell Therapeutics.
Side-by-Side
Relies on mannose-6-phosphate receptor (M6PR) for cellular uptake
Low uptake efficiency in skeletal muscle, kidney, heart, lung
Requires high doses and biweekly IV infusions
$300K–$750K per patient per year
Patients still face progressive disability
Engineered IGF2 tag binds to more abundant receptor pathway
5–10× higher uptake in hard-to-treat tissues
Reduced effective dosage, improved safety
80–90% lower manufacturing costs
Applicable to both classical ERT and gene therapy