YSM Issue 91.3

UNDERGRADUATE PROFILE
RACHAEL PUTMAN (TC ’19)
WHAT COMES BEFORE BABY STEPS?
BY HANNAH RO
PHOTOGRAPHY BY CARLI ROUSH
Rachael Putman tests the safety and efficacy of triplex gene editing
technology, which uses peptide nucleic acids.
Designer babies, genetic remodeling, risks in clinical trials: in
today’s rapidly evolving field of biomedical engineering, ethical
dilemmas rage. But for Rachael Putman (TC ’19), it’s simple:
“The whole point of medicine is to help people heal. If we can
take gene editing and make it do that in a safe and effective way,
then it’s something that we should pursue,” she said.
Putman, a Missouri native, matriculated to Yale College
without any prior research experience, but was quickly hooked
by Professor Mark Saltzman’s master class on in-utero brain
research. She reached out to Saltzman for a position in his lab,
and took her first steps in research. After honing her technical
laboratory and research skills under Saltzman’s tutelage, Putman
began investigating in vivo gene editing in mouse fetuses
alongside Adele Ricciardi, an MD-PhD student at the Yale
School of Medicine.
As a collaborative effort between the Saltzman laboratory
and the laboratory of Professor Peter Glazer, Putman and Ricciardi
are testing the safety and efficacy of triplex gene editing
technology, which uses peptide nucleic acids (PNA). Unlike
other gene editing techniques, such as CRISPR and TALEN,
PNAs allow for a safer gene repair by avoiding double-strand
breaks in the host DNA. Once the PNA is safely inserted into
the cell, it binds to the targeted mutation in the DNA and creates
a triple strand. The cell then recognizes and removes the
PNA-bound segment from the genome, creating a gap. A short
piece of DNA delivered with the corrected base pairs is then
used as a template to fix the gap created by PNA.
“We tried to focus on safety and see if we were getting any
off-target effects,” Putman said. “Through our analysis, we
couldn’t find any, which may give it an advantage over other
technologies like CRISPR.”
Putman and Ricciardi apply this gene editing pathway to cure
human models of disease, such as cystic fibrosis, β-thalassemia,
and sickle cell disease, in mouse fetuses. Nanoparticles that contain
PNA strands are delivered to mouse fetuses and the mice
are tested for the absence of disease after birth. “We were able to
show that we got disease improvement after birth; the mice were
healthy when they were born,” Ricciardi said.
A successful direction in this project led Putman to an even
more fundamental question: can we do this even earlier? In
other words, if site-specific genome editing works in fetuses,
could it work in single-cell embryos? In many genetic diseases,
organ damage can take place early on during the fetal stage of
development. However, these diseases can often be identified
at the embryonic stage if a mother undergoing in vitro fertilization
chooses to screen for genetic diseases before implantation.
If gene editing can be performed within the first days of
life, there is a possibility that the fetus will undergo completely
healthy organ development. With hopes of clinically translating
her work with mice embryos, Putman embarked on her
own project: Synthetic Nanoparticle Delivery to Mouse Embryos
for Site-specific Genome Editing.
For her work with these two projects, Putman received the
Arnold and Mabel Beckman Foundation award in 2017 and
presented her work at the Beckman Scholars Annual Research
Symposium for the following two summers in Irvine, CA. Putman
was one of two Yale College students in the class of 2019
to receive this distinction.
Outside her research, Putman is the president of Demos, a
service group that makes science education more accessible
to students in New Haven public elementary schools. She
also teaches a class about genetics to neighboring middle and
high school students through Splash at Yale. As Putman serves
younger scientists through her volunteer work, she attributes
her own successes to mentorship. “I had two really wonderful
teachers throughout middle school and high school,” Putman
said. “What they taught me was that we all have things we’re
good at and are passionate about. What is more important is to
follow your passions and see where they lead you.”
36 Yale Scientific Magazine October 2018 www.yalescientific.org