To gain extensive insight into the differing perspectives of stakeholders, we first identified the stakeholders involved in our project.

We started by collecting data from the public about their understanding and perception towards gene therapy and genetic engineering to understand the ground knowledge. Through this data-driven approach, we identified misconceptions people had about genome editing. To better address these misinterpretations of the public, we sought the feedback of scientists in the research field and ethics regulatory board in Singapore. All these are documented in #CasAsks.

After the team decided on genetic editing as a broad topic, we were exploring between the well-researched DNA editing and the uprising RNA editing field. We investigated both the technical risks and ethical concerns arising from our project. These are some key opinions we heard from the experts/scientists that affirmed our choice to zoom into RNA editing.

Dr Kon Oi Lian: “RNA editing, because of the nature of RNA, I think should be safer because any adverse effects do not last forever. In terms of RNA editing, the ethical issues would be less complicated compared to DNA.”

Dr Calvin Ho: “RNA editing, at least the changes would be more transient than permanent. It would be interesting depending on the condition that we are intending to address. If it’s able to alleviate some of the safety concerns and prove a measured way forward, I think that will be extremely beneficial to holistic development. ”

Thus, after understanding the ethical conundrums surrounding genetic engineering, we chose to embark on transient RNA-editing as opposed to permanent DNA-editing due to the lesser concerns of non-permanent edits and hence a higher likelihood of public acceptance. Our fundamental research on RNA editing would contribute to the development of RNA-related diagnostics and/or therapeutics, which likely faces less ethical criticisms of infringing the sanctity of genetic material. Quoting Dr Kon, “Inflammatory conditions, infectious conditions, which of their very nature last only for days to week might be a good area in which RNA editing could be helpful because the effects is over when the infection is over. You need not worry about leaving a footprint in the person or the cells you have modified. "

As with all technological applications, there are definitely inherent risks. By talking to scientists working in the field of genetic engineering, we evaluated the possible sources of risk in our project and sought to alleviate these risks. We identified 2 main sources of risk stemming from our research: A main source of risk for this research is the off-target effects of the guideRNA, which would hinder the specificity of editing.

Quoting Dr. Autios, “When you design everything really well –you get the perfect guideRNA and use the best available Cas enzyme which has been improved in specificity, it can work very precisely.” With this, our modelling team came up with a guideRNA-designing programme that identifies the Kozak consensus sequence and makes a suitable guideRNA from it. Thus, this possibly decreases the likelihood of off-target sequences and improves the binding specificity. This is a technical issue related to our technology and the aim for modelling is to reduce the off-target risks to the largest extent possible.

From our #CasAsks public opinion survey, we uncovered misconceptions and knowledge gaps that are rampant in the public. We identify the public as the greatest stakeholder as they are the eventual consumers of such genetic manipulation technology. Acting upon formative feedback obtained from the public, we dedicated majority of our human practices efforts into educating and engaging the public. Recognizing the need for enhanced scientific literacy and to generate discussion about genetic engineering, we had 3 target groups and action plans in mind:

#CasTalks – a series of videos targeting the public. We present a diversity of perspectives, from the application and potential of genetic engineering to the ethical concerns. We hope to dispel misconceptions and bridge knowledge gaps. This encourages members of the public to adopt a more informed stance, and further engage with government bodies to navigate the ethics with scientific advancement.

#CasTeaches – a series of outreach talks with the aim of garnishing students’ education with technicalities, therapeutics and diagnostics of gene editing. More so than the public, students need to be cognizant to such prevailing technologies that will be of increasing relevance to them in the future.

#CasWrites – a series of in-depth opinion-based discussion targeting readers who want to engage in more critical thinking and be exposed to theoretical epistemology behind ethical frameworks.

By coming up with 3 separate branches to target a diverse audience, our team hopes to be able to engage people of all walks of life and varying degree of knowledge in genetic engineering to gain insights on this topic. We also hope to develop their positive attitudes towards scientific research.