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U CHEMIST LEADS MATCHUP AGAINST GENETIC DISEASE by L AUREN WIGOD Writer Intern
CARRIE WAGER, PHD’00,
love having a phenomenal team that I
mature RNA, which leaves the nucleus.
RECIPIENT OF CHEMISTRY’S
work with.”
But the process of going from pre-
2020 DISTINGUISHED ALUMNI AWARD, HAS ALWAYS VALUED TEAMWORK WHETHER ON THE SOCCER PITCH OR IN THE L AB.
While studying at the U, she researched total synthesis of natural products in Gary Keck’s lab and played on an intramural soccer team where she met her husband. Wager is a chemistry midfielder in her career, driven to cover a lot of ground by her passion for working in a fast-paced, team environment. After graduating from the U, she spent 17 years at Pfizer as Senior Principal Scientist, Director of Business Planning, Chief of Staff for Pfizer Medical, and Medical Strategy Lead in Oncology. Then she earned her MBA from MIT in 2017 before joining Ascidian Therapeutics. “I really found the place where my heart belongs, and that’s working in startups,” she says. “In those situations, it’s pretty high risk, but also high reward. The strength of the team is critical, and I really enjoy that part. I’ve always been into team sports. I
EXON-EDITING IS THE NAME OF THE GAME
The team Wager currently works with at Ascidian is taking a new approach to gene therapy, influenced by the organisms that the company is named after. Wager says, “We were inspired by what happens with sea squirts or ascidians because they re-engineer the transcriptome. They start as creatures that are free-floating … but then they become these structures after they re-engineer their transcriptome and are fixed on the bottom [of the ocean].” As sea squirts
mRNA to mature RNA is the excision or the cutting out of introns.” The splicesome is the enzyme responsible for removing the introns and leaving the exons which are then joined to form the mature strand of RNA. Ascidian designs molecules to target mutant exons and replace them with a wild-type version. “We use these molecules that are packaged in an adeno-associated virus to gain entry into the nucleus. Then those molecules are built to bind to specific locations in messenger RNA. … The
(Ascidiacea) mature, they self-edit their messenger RNA to change the proteins that are expressed and, ultimately, their structure. Ascidian’s strategy for fixing genetic diseases in humans is different from other existing methods of gene therapy because it works by editing RNA through a process that is already inherent to the cell. “DNA is transcribed into RNA in the nucleus,” Wager explains. “It’s initially transcribed into pre-messenger RNA (pre-mRNA) and pre-mRNA becomes
STUDENTS & ALUMNI | 2023
