The State of the Drug Development Pipeline

A therapeutic approach using a virus (non-infectious adeno-associated virus) to deliver a functional UBE3A gene to cells inside the body (in-vivo).

• MVX-220Funded by FAST
• SKY-AS
• UNC
• FASTFunded by FAST
• LatusFunded by FAST

A therapeutic approach where an individual’s own bone marrow stem cells are removed from their body, modified outside the body, and then returned to the body with a new, functional copy of the UBE3A gene. Once the bone marrow cells are injected back into the individual, they grow and repopulate, with the goal of those cells continuously supplying the body with a healthy version of the UBE3A protein.

• ube-cel TMXFunded by FAST

A therapeutic approach replacing the missing or nonfunctional UBE3A protein in the brain.

• KGIFunded by FAST

A therapeutic approach that uses modified RNA or DNA to bind to the UBE3A-ATS (UBE3A antisense transcript). Typically, the UBE3A-ATS silences the paternal UBE3A gene. By binding to the UBE3A-ATS, the ASO could stop the UBE3A-ATS from silencing the paternal UBE3A gene, enabling UBE3A protein to be made.

• Ionis • obudanersen
• Oak Hill Bio • rugonersen
• CaltechFunded by FAST
• Yale

A therapeutic approach using engineered proteins constructed to bind to specific DNA sequences to regulate gene expression. ATF-Zinc fingers use zinc ions to stabilize their structures giving them a finger-like appearance. ATF-ZFs can bind to the UBE3A-ATS and prevent the silencing of the paternal copy of the UBE3A gene, enabling UBE3A protein to be made.

• UCDFunded by FAST

A therapeutic approach that recognizes a specific section of DNA or RNA and then cuts at that specific section. This approach could be designed to cut the UBE3A-ATS and potentially allow the paternal UBE3A gene to be turned on.

• CourageASFunded by FAST
• Arbor Bio
• UNC
• CHOPFunded by FAST
• Modalis

A therapeutic approach using pieces of RNA, such as micro-RNA (miRNA), short-hairpin RNA (shRNA), or small interfering RNA (siRNA) that are aimed to bind to the UBE3A-ATS and prevent the silencing of the paternal copy of the UBE3A gene, enabling UBE3A protein to be made.

• Encoded • ETX201
• MGHFunded by FAST

A class of therapeutics where the compound is small, enabling it to easily get into tissues and cells and interact with proteins, DNA, RNA, or the ATS.

• UNC

A therapeutic approach to upregulate (turn-up) a specific gene. It uses similar components as traditional CRISPR, but does not cut the DNA or RNA.

• UCSFFunded by FAST

A therapeutic approach in Angelman syndrome that focuses on the pathways and proteins that are negatively affected when UBE3A protein is missing or non-functional, rather than focusing on UBE3A directly.

• Neuren • NNZ-2591
• Healx • HLX-0553
• BIOM • BIO017
• Brown • OPCFunded by FAST
• Brown • SYN-3Funded by FAST