Grupo Loeffler-Russek

Enrique Blanco

Why taking about CRISPRC9?

Talking about Genomics, since 1987 a technique named CRISPR C9 (Clustered Regularly Interspaced Short Palindromic Repeats) was discovered by Y.Ishino and letter by F.Mojica, the method used on the bacteria, practically the CRISPRC9 is to cut a small part of the DNA which affects the replication by the virus, therefore, to avoid infection of a virus,as expliained themethod was about stopping the replication of Virus DNA using a protein (C9) that identify certain RNA chain and cut and replace using C9 so it is easy to use the technology, after that the Dra. Jennifer Doudna applied the technique on sickle cell disease with satisfactory results.

The CRISPR method allows us to cut a DNA chain, and replace it with another sequence that will change a caractheristics of the individual and his next generations, the problem is that it might change another similar part of the DNA chain if there is a similar repetition of the sequence.

This results open a huge range of possibilities in customized medicine,  this techique, recently on December 2023, the FDA approved the CRISPR technology for sickle celldisease treatment.

On that context, there is a huge change on the regulatory authorities, accepting a DNA technique to resolve a disease, so opened a possibility to clinically investigate changes of certain genes that provoque diseases, the problem is to demonstrate that the changes doesn’t have any other impact on gene transcription and therefore any other impact on genes, we have to be aware that even this good results might be modified a gene that is not expressed, it’s recessive character, so might be expressed in a future condition, on 3rd or 4th generation of people from that familiy, and was not entirely demonstrated by the clinical studies.

On the other, hand this also opened a lot of possibilities to have discussion on the ethical aspects, regarding, first what is the purpose of the investigation using this technique, do we have identified the gene, is the technique well directed to this gene? Is it possible that might cut another genes? Do we have control on that results?  Do we allow this technique to be used for which diseases?, at Mexico in the Health General Law (Ley General de Salud) on article 317bis) established that all organs and tissues shall NOT be carried out from the Mexican territory (its prohibited) and must be part of an approved investigational study by the authorities.

In the same line of discussion, the human genoma is protected by the law as part of the confidential particular information, so any person has to permit the use of their own genomic information. The Helsinki declaration also provides an international guide to protect the human individuals from clinical studies, the informed consent also cover the individual permission to use your genomic data, but depending on the trial might be consider a violation of the declaration and the informed consent might not cover the future generations.

If we think on that, it might be possible to ensure that a scientific study using the CRISPR C9 method to identify genes that provoque an speficic cancer that might be stopped, but it affects another genes which are not expressed but will be on 2 or 3 g next generations, so it is ethical to accept the treatment for the benefit of the patien but potentially affecting future individuals? Is the right to consent for a treatment also implies your entire future generations? Do we have to include the statement on the informed consent? Is it legally accepted? Will be accepted in all countries, do we have to promote a legal initiative to cover the CRISPRC9 method at the World Health Organization, as region, country, district, etc..

Regarding the clinical studies to trial the technique, are they safe? What we need to include in the informed consent?, as the sponsor what are the legal responsibilities? The patients rights are covered? Do we have to extend the informed consent to next generation? 

Is the decisión maker rights to cover next generation, even if they don’t know if they want to marry? Do we have to include a disclosure element regarding this CRISPR technology use before marry?

On the science perspective, this is a super advance, not only by the method itself discovered in 1987, but also to continue studying how we can modify our own genes to make better life’s, also on agriculture enhancing nutrient properties on whole alimentary industry, on the species protection or elimination this opens and huge change also, we can modify a certain characteristic to eliminate a plague, only by modifying the genes of  a small population that will be introduced into the plague population, so we have the potential to destroy an entire species of the planet.

If we think this potential, we also have the possibility to enhance any species on the planet including ours.

Is it possible to use this technology CRISPR C9 at war? Is it possible to control? How are we going to control it?, do we have to start initiatives from the United Nations Organization, when is going to happen, is it started?, all countries are represented? How we will control the non ethical use at the world?

On the health perspective, it is an important change, we as a country, can target certain diseases that are the most impacting and perform studies to resolve it, so identifying the most important diseases, the genetic markers and make the cut and repair as needed of the genes, then eliminate the disease, evaluate the population statistic to ensure population health and pharmacovigilance monitoring.

So, from the country perspective we can consider that we can universalize the medecine for the entire country on the most important diseases targeting either the human genes or the vectors (viruses, bacteria, etc), how are we going to control or manage the studies to ensure the benefit?, what are going to be the rules or legal requirements to ensure appropriate – ethical studies that benefit the population, how are we going to separate the Finantial benefits from companies vs countries, are we going to have a regulation to ensure benefits to all stakeholders?.

On the other hand, for specific diseases the disease will be targeted per individual, so the advance therapies using CRISPRC9 technique will growth from now, so the rare diseases are going to be investigated, the cure will be hold by a country? By a company? Is it possible to patent it?…

If we include the AI (Artificial Intelligence) I see a huge possibility to predict using the artificial intelligence considering the genes disease information, pharmacovigilance, how molecules work and how the cells interact between them, how the CRISPRC9 method will shall be used, can we target better? Do we have to regulate and how the regulation should work on countries, region or worldwide.

At LATAM region will follow the FDA on this approval, are we prepared regionally to ensure ethical use and technically prepared, an international committee shall be related to administrate the scientific studies, legal and regulatory perspective, definitions on how the process might be to regulate and ensure ethical behavior.

Regarding the regulatory reliability and regional acceptance is the CRISPRC9 technology accepted in all countries?, a lot of questions will be discussed prior approvals as region.

The CRISPR C9 technique and the AI together potentialized the possibilities, and the regulation shall ensure appropriate and ethical use of the technology, different perspectives discussions by committees, we can reach a better and safe place to life.