Project seminar with the professors and students of Tsinghua Xuetang
Tsinghua Xuetang Talents Program is an experimental program providing intensive academic training
for its members, which selected students with promising creativity and ambition in an academic
career in basic sciences. As our project largely involves application of a new tool in fundamental
biology, we decided to hold a lunch seminar with teachers and students of Tsinghua Xuetang Talents
Program to present and consult on our project, getting advice from talented peers in life sciences.
Our discussion involves three topics: the technical feasibility, safety, and bioethics issue
concerning our project.
CRISPR/Cas9, a promising new tool for nucleic acid manipulation, is becoming familiar to most bio-majors.
Reasonably, the off-target effect of this system was considered to be a potential flaw in our
project. Suggestions to solve this problem included the application of serial or overlapping sgRNA,
careful quantification of the system and so on. Concerning the details of the model we built for
quantification, we were grateful for a lot of helpful advice we received.
Many expressed their concern about the safety of our gene mutation surveillance system, as it was
supposed to interfere with gene expression process in living cells.
“I think that your project should really do more to control the system, keeping it running in a
proper way. Various interactions could happen in vivo, which should be observed before the
system was put into application.”
“The major problem here is the absence of a switch or brake, which could shut down the whole system
in a proper time. I think at least a stop button is necessary, and I would suggest you add multiple
layers of control and a reversible switch to achieve more precise temporal control. The surveillance
system doesn’t have to be constitutively active.”
Together we came up with several possible approaches to improve the safety of our system.
Though the experiment we designed was only sufficient to attain a proof of concept, the design of our
system has a broad perspective of application, identifying specific sequences in the transcriptome.
However, one major goal of our system, which is to target hotspot mutations to prevent diseases like
cancer from the very beginning, requires the modification of the organism genome.
Opinions diverged on this issue. As is well known, the modification of our own genomes has always been
a controversial issue that calls for sufficient consideration of law, policy, ethics, supervision and
safety control. We discussed intensively on this issue. In general, most of the participants expressed
approval of its use in experimental systems like cell culture or model organisms, but only a small
number were supportive for its application in human. For now, the major clinical field involving
manipulation of human genome is gene therapy, which is still beginning. The preventive application
of our system to human remains to be examined.
* The modification of our quantification model;
* The addition of safety control termination in our design;
* The consideration of bioethics issue