Motivation

After our survey, with the public concerns that we collected, we want to interview the last stakeholder in our conversation, the  professional doctors, as they are the ones utilizing gene therapy in the future, therefore it is important to know what their attitude towards gene therapy is. They also know the needs of the patients from a professional standpoint rather than an emotional one, so they are able to provide us with valuable suggestions to address issues with the patients.

 Professor Denise Goh

Professor Denise Goh is a Senior Consultant and heads the Division of Pediatric Genetics and Metabolism at the Khoo Teck Puat-National University Children's Medical Institute, National University Hospital.

She holds an optimistic view of gene editing, especially using AAV and CRISPR-Cas to treat genetic disorders. She hopes that gene editing can be made available in five years’ time, and to replace traditional methods of treatments, which are comparatively ineffective or cumbersome. For example, the enzyme replacement treatment for Hemophilia, she pointed out, requires the patient to receive the treatment continually and also posed to the possibility of a severe immune response.

When asked about DNA editing and RNA editing for disease treatment, she thinks that DNA editing has a major advantage over RNA editing, which is a relatively lower cost. As RNA editing needs to be tailored to the individual patient, and the effect is not as durable as DNA, the cost for customization and continual treatment would make it more expensive. On the issue of safety, she is not worried too much on that of DNA editing, as she believes that RNA editing, whose effect being transient, is also able to cause a severe immune response and result in organ failure in a short time. While the negative effect of DNA editing is long-lasting, its advantage of fixing the gene permanently, in her view, outweighs the potentially disastrous effect. 

In spite of that, she also finds value in RNA editing — for cancer treatment, some are analyzing transcriptome to identify the disease-causing transcripts, one layer about protein profiling, because the same gene can produce multiple transcripts due to alternative splicing, therefore, when the genome is not erroneous, and when defective proteins are too many to be corrected, it is important to identify the transcripts and correct or knock down them. The major problem now, she asserts, is that RNA is very unstable as compared to DNA or protein, and the transcriptome changes from time to time, from cell to cell, making it especially hard to anal

 Training Doctors from Duke-NUS Medical School 

We also interviewed training doctors Dr. Tracy Koh and her fellow colleagues from Duke-NUS medical school to see how future doctors view such an issue. 

Figure 7. Photo of our interviewer with training doctors

We raised the issue of safety to the interviewees, and they agreed that safety is indeed a big issue as the patients would be worried about the risks of receiving the treatment, especially when it is not so well-tested at this stage. From a technical point of view, apart from efficiency issues related with CRISPR-Cas, delivery system would also be a problem where target cells may not be reached. Only by having enough clinical trials can we ensure the safety level, which takes a long period to accomplish. From the public’s aspect, they may not have sufficient basic information about the risks related to gene editing. There are public concerns with GMOs, not to mention having their own genes altered, as one of the interviewees mentioned. Therefore, public education is needed to establish a more objective view towards gene editing instead of a subjective one fueled with fear for change.

When we asked about the issue of cost, they affirmed that cost is going to be inevitably high at the early stage, due to the fact that the technology is still at its early stage — even sequencing was very expensive at the start, one of the training doctors added. The general view towards cost is optimistic as they believe that as the research progresses, gene therapy will eventually become more affordable.

On the issue of DNA and RNA editing, they hold the view that both are important and it will depend on the particular disease. For a life-threatening disease such as cancer, DNA would be a better option while for a less severe disease with short-term effects, RNA editing might be a better option. Since most patients would have no idea of what DNA editing or RNA editing is, it would be important that the doctors have professional knowledge and advice the patients the best method according to the need of the patient. It is the patient who makes the ultimate decision, so it is equally important that the patients have some basic understanding of different forms of treatment.

 Our Takeaways

Both DNA and RNA editing have their own values, as each has a unique advantage under different situations. Since gene therapy is still a rather unexplored field, we cannot be sure that one will definitely work better than the other. Therefore, we should research in both areas, especially gene editing on the RNA level, which is less developed and researched as compared to DNA editing.

Currently, DNA editing is likely to be preferred due to the possibly larger cost incurred from multiple treatments of RNA editing. In order to not limit ourselves to DNA editing only, we seek to reduce the cost of treatment at the very early stage — disease analysis. We could develop an easier sequencing technique and make it more affordable to identify the genetic mutations since current transcriptome analysis is too time-consuming and complicated.