October 2017
Volume 1, Issue 7

For the October OPDA newsletter, Robert Hermosillo, our Ripss officer wrote a highlighted commentary about the recent study lead by OHSU researchers in Nature that demonstrates that the CRISPR method may repair genes in human embryos preventing inherited diseases.

OHSU pushes gene-editing techniques into the human realm

by Robert Hermosillo, M.S., Ph.D.
October 1, 2017

Researchers at OHSU lead by Shoukhrat Mitalipov, PhD. at the Center for Embryonic Cell and Gene therapy, successfully tested a gene-editing technique in human embryos. Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR)has been upending the genetic community by allowing for a low cost and effective of targeted genetic modification. Although, CRISPR has been used in many model organisms already, the study "Correction of a pathogenic gene mutation in human embryos" serves as proof-of-concept that the technique works to reduce correct heritable disease.

The study aimed to correct a MYBPC3 mutation (heterozygous dominant 4-bp GAGT deletion in exon 16) responsible for a specific type of heart disease, hypertropic cardiomyopathy, which is characterized by left ventricular hypertrophy, and myocardial stiffness. This genetic disease is estimated to be present in 1:500 adults who present with cardiac failure. In the current study (Hong Ma et al. Nature 2017), the OHSU team inserted short DNA strands of the healty (non-mutated) sequence, then used the embryo's capacity to repair and cut the mutated DNA, using this healthy copy as a template. Previous attempts by a Chinese research team at using CRISPR in human embryos have been met with mixed results for their lack of specificity, which lead to mosaicism , where some cells expressed the healthy gene, and others expressed the pathological gene. To increase the efficiency of this method, the team injected the CRISPR system at the same time as the sperm into the egg, hoping to prevent expression of the pathological MYBPC3 copy before cellular mitosis.

Results demonstrated that of the 58 embryos tested, 72% of the cells managed to express the healthy MYBPC3 gene (compared to 50% expected by chance).Notably, the team was unable to find any evidence of off-target mutations.

Naturally, The worldwide scientist community is concerned about the relative ease of implementation of genetic modifications. Considering all the complex ethical issues brought by this study, the National Academy of Sciences and National Academy of Medicine released new criteria to provide clinicians and policymakers some direction on CRISPR research. This technique is so effective, that the speed at which the science is advancing is pushing the boundaries of society's ability to fully understand the ramifications of this work. Since these modification will affect a person's whole genome, and they will be carried on to their offspring for further generations. 

Aside from complex ethical concerns of where this research could lead us, other researchers have voiced methodological concerns as to whether or not the egg and sperm would be close enough to share genes, and proteins for genetic expression, or if the embryos managed to develop from the maternal DNA alone, or that the cuts in the genome were made, but not replaced with the healthy version of the gene.

However, this paper provides an important step towards disease prevention by removing them from the individual, and consequently, the population. The race for the CRISPR cure just started, so this research has a long way to go before it can be could be used in a clinical setting.