In November 2018, a Chinese researcher He Jiankui, claimed to use Crispr-Cas9 to genetically modify baby twins. He made the announcement on the eve of the Second International Summit on Human Genome Editing in Hong Kong, a fitting venue. By directing Crispr-Cas9, he claimed to have used in vitro fertilization to create human embryos in whom he deliberately disabled the CCR5 gene, which makes the protein that HIV utilizes to enter into cells.
The editing of first human embryos in a lab petri dish was done in 2015and it wasn’t until 3 years later that scientists were able to genetically modify human beings. The first possibly successful experimentation has led for approval of the first lawful human trials for Crisprto potentially cure inherited blindness.
First, what is Crispr-Cas9 and how did we first come about it? This was first discovered in bacterial cells, whom utilize it as a natural defense mechanism. Say for example, a bacterium is invaded by a virus. The bacteria capture snippets of DNA from the invading virus and uses them to create DNA segments known as Crispr arrays, which it integrates into its own DNA sequence, allowing it to remember the virus. If the same virus attacks again, the bacteria produce RNA segments from the previously integrated CRISPR array to target the viruses’ DNA and it utilizes Cas9 or a similar enzyme, to cut the virus DNA apart, disabling it.
In Crispr-Cas9 works similarly in the lab: researchers create a small piece of RNA with a “guide sequence” that binds to a specific target DNA sequence in the genome. The same RNA is also bound to the Cas9 enzyme. Once the modified RNA recognizes the DNA sequence, the Cas9 enzyme cuts the DNA at the targeted location. Once cut, the cell’s own DNA repair machinery is utilized to add or delete additional pieces of genetic material or to make changes to the DNA by replacing an existing segment with a customized DNA sequence.
The Theoretical Application
So how can this be utilized for human diseases? Theoretically, it works ideally for diseases that are caused by single genes, such as Wiskott-Aldrich Syndrome, an X-linked disorder, in which a mutation in one gene leads to abnormal expression of the Wiskott-Aldrich syndrome protein, whose expression is limited to cells of the non-erythroid hematopoietic lineage, leads to the clinical phenotype of eczema, thrombocytopenia, and immune deficiency. If this gene was to be “corrected”, Crispr-Cas9 would be the technology to do so, and potentially cure the disease!
The Lawful Clinical Trial
The first trialto potentially cure one form of Leber congenital amaurosis, the most common cause of childhood blindness, occurring in about 2 to 3 of every 100,000 births, has already started the recruitment and is to potentially start on 3 September, 2019.
The FDA first gave permission for this genome editing trial on 30 November, 2018. It has allowed Editas to test EDIT-101 therapy, which is designed to correct a point mutation in the CEP290 gene, the IVS26 mutation, that leads to correct splicing of the CPE290 transcript and dysfunctional CEP290 protein, which is thought to play a structural role in the cilia of light-sensing photoreceptor cells in the retina.
This trial will be a nonrandomized open-label single ascending dose study that will include 18 participants from ages 3 to 17, whom will be enrolled in up to 5 cohorts to evaluate up to 3 doses of the drug that consists of the aforementioned Crispr-Cas9 technology. The expected completion date for the study is March 2024.
If successful, I believe this trial will be a catalyst to future trials for genomic editing. I wonder how long it will take for the human species to widely accept genomic editing and realize its potential as the fountain of youth.