CRISPR-Cas9: A CURE FOR NOONAN SYNDROME?

CRISPR-Cas9: A CURE FOR NOONAN SYNDROME?

‘Your child has an incurable disease’ is a statement that every parent fears but unfortunately for parents of children with Noonan Syndrome (NS), it is one that they have heard from medical professionals. Such a statement understandably triggers emotions of despair, anxiety, depression and possibly most of all – powerlessness.

As parents we want our children to be able to achieve and accomplish anything they desire and for their world to be one of infinite possibilities. Unfortunately when it comes to having children of their own, individuals with NS carry a 50% chance of ‘passing’ NS to their offspring.

Thankfully a new revolutionary technology called CRISPR-Cas9 now gives us the ability to prevent passing on hereditary genetic diseases (such as NS) to future generations and cure some genetic diseases altogether. CRISPR-Cas9 is a gene editing technique that allows us to safely and precisely alter, delete and replace DNA within an organism.

WHAT IS CRISPR-Cas9 & HOW DOES GENE EDITING WORK?

Editing genes can mean removing or replacing an existing gene, switching a gene on or off, or inserting a new gene altogether. Whatever the aim, the first step is always to find the target DNA that codes for the gene and grab hold of it, so a cut (or ‘edit’) can be made.

CRISPR not only finds the target gene and locks on, it also delivers an enzyme that cuts the DNA. And it does all this with unprecedented accuracy. The reason it’s able to manage this precision double act is because CRISPR is made of ribonucleic acid (RNA) — a molecule that can be tailor-made to perfectly match a sequence of DNA or to bind to a protein.

CRISPR RNA does both jobs — one end is custom-made to match the target gene’s DNA sequence, and the other end binds to a DNA-cutting enzyme, or nuclease (Cas9).

CRISPR is not man-made; it’s actually from bacterial immune systems. When a virus invades a bacterial cell, it leaves traces of its DNA in the bacterial genome. If the bacterium encounters that virus again, CRISPR RNA uses the viral DNA remnants and an enzyme (nuclease) called Cas9 to attack the virus.

An improved version of this natural CRISPR-Cas9 combination is now being used in gene editing research in laboratories around the world.

GENE EDITING AND NOONAN SYNDROME

Currently the only way to prevent passing on autosomal dominant genetic diseases is a process called Preimplantation Genetic Diagnosis (PGD). Embryos are screened and those free of disease are selected for implantation in the uterus. PGD is an expensive technique in what is already an expensive process (IVF) but PGD has already been successfully used to prevent the inheritance of diseases such as Cystic Fibrosis, Turner Syndrome and could be utilised for NS.

PGD essentially ‘picks out’ the non-defective embryos. Where CRISPR-Cas9 gene editing is revolutionary is in the way it would allow doctors to genetically edit ‘out’ the gene mutation responsible for NS in ALL embryos pre-implantation; dramatically boosting the chances of a successful non-NS pregnancy and delivery.

THERAPEUTIC IMPLICATIONS & APPLICATIONS

Outside of NS and other inherited diseases, gene editing has almost limitless applications.

CRISPR-Cas9 could treat and prevent diseases by removing and replacing the faulty gene (e.g. haemophilia, cancer, Type 1 diabetes). Such interventions would not only improve life quality and duration for patients but save families, governments and medical institutions billions and possibly trillions of dollars in medication, rehabilitation services and economic productivity. Gene editing can alter ecology by introducing disease resistant animals (e.g. Zika, Dengue or malaria free mosquitos) and gene edited crops can be modified to boost crop yields or prolong produce life which will feed more people and reduce waste. Genetically modified crops can be created to be pesticide or herbicide resistant – making them more profitable for farmers and safer for consumers and the environment.

CURRENT USES

CRISPR edited mushrooms and tomatoes that don’t ‘brown’ have already been approved for consumption in many countries. CRISPR-Cas9 wheat that is resistant to mildew is already commercially available for farmers.

CRISPR-Cas9 has already been shown to cure Huntington’s Disease and Muscular Dystrophy in mice. Gene editing has also been used to remove over 60 viruses from pigs to reduce the rejection of pig organ transplants in humans.

Large scale human trials are still some time away but researchers have had success in removing HIV from human DNA cells using CRISPR-Cas9.

In 2016 approval was also given to a British researcher to use CRISPR-Cas9 on unwanted IVF embryos to better understand the role of genes in healthy development.  The researchers will use unwanted IVF embryos and the experiments (and embryos) will be terminated after one week.

In November 2016 a Chinese medical research group injected CRISPR-Cas9 into a person for the first time. The researchers removed immune cells and disabled a protein which limits immune responses hopefully reducing the cancer growth rate.

In March 2017 a Chinese team used CRISP-Cas9 to correct genetic mutations in multiple embryos. In the first experiment three embryos were genetically edited to remove a mutation that triggers a serious allergic reaction to certain foods called favism which destroys red blood cells. In two of the embryos the mutation was corrected successfully. The second experiment involved editing and repairing a beta-thalassemia mutation in four embryos. The mutation was successfully repaired in only one of the four embryos.

In March of this year French doctors used genetic editing to cure a teenager of sickle cell anemia. The doctors removed the faulty gene that was interfering with haemoglobin production and inserted a functional gene. The teenager has been producing ‘normal’ blood for 15 months – he is now considered ‘cured’.

ETHICAL QUESTIONS

What are the Ethics of genetic manipulation?

Despite the overwhelming scientific evidence that GM foods are safe for consumption, many people fear genetically modified foods or technology.  Opponents of GM argume that GM foods are ‘transgenic’ – meaning scientists have combined the DNA of different species to produce a new trait or ‘genetically modified organism’ (GMO) that would never have occurred or been created naturally. CRISPR-Cas9 appeases this opposition as it allows genes to be edited and new DNA created without introducing DNA from foreign species.

There are also the long term implications to consider. If a germline is altered then that new trait will be passed on forever in future generations and the consequence of such long term intervention may be difficult to currently ascertain.

Based on concerns such as these, The International Summit on Human Gene Editing in Washington in December 2016 resulted in a call for a moratorium on using CRISPR on germ line cells (egg and sperm) until all safety issues and societal concerns have been addressed. This moratorium has not been observed.

Regardless of the ethical or philosophical questions raised by such technologies no one can deny that having the ability to prevent, treat and eradicate disease and improve lives is an exciting prospect and gives sufferers of genetic and currently incurable illnesses great hope for themselves and their children.