Clustered Regularly Interspaced Short Palindromic repeats (CRISPR) technology, allows precise gene editing that can correct mutations or otherwise alter the human genome. By altering genes in human embryos, specifically gametes (oocytes and spermatozoa) used to create embryos, scientists and clinicians using CRISPR have the capacity to remove genes in order to prevent genetic disease.
CRISPR uses short segments of prokaryotic DNA (generally 24 to 48 base pairs in length) with specific and known repeating nucleic acid nitrogenous base sequences. Spacer DNA introduced from viruses or plasmids separate the repeating sequences and the segment finds and binds only to pre-designated DNA sequences. First discovered by Osaka University scientist Yoshizumi Ishino in 1987, CRISPR technology allows scientists to cleave specific and cut DNA molecules at specific locations. This ability to cut with precision allows precise removal of genes and the precise insertion of new genes in the same place. The removal and addition of genes is termed CRISPR interference and such interference can create new lines pre-embryonic germ cells and new verities of crops.
CRISPR -altered sequences are new a common feature of some prokaryotes (cells, including bacteria and viruses, without a true nucleus). The removal and addition of genes is termed CRISPR interference and such interference can create new lines pre-embryonic germ cells and new verities of crops.
CRISPR technology has been used to edit the genome of plants, mice, monkeys and human embryos. CRISPR technology can also be used to create programmable transcription factors that allow genes to be specifically activated or silenced.
The latest generation of CRISPR technology relies on the use of the Cas9 enzyme called Cas9 to cut or snip targeted gene sequences surrounding a defective gene. If a healthy normal gene is present in the DNA inherited from the other parent the embryo repairs the break where the mutant gene was previously located by using a template copy of the normal or healthy gene. The embryo then continues cell division with only healthy normal genes.
The techniques applied can potentially eliminate thousands of heritable diseases both from family lineage and the human syngameon (the entire population). Parents carrying mutations that cause heritable diseases like Huntington's and Tay-Sachs could potentially eliminate the chance their child will inherit disease-causing mutations.
In August 2017, researchers at the Center for Embryonic Cell and Gene Therapy at the Oregon Health & Science University (OHSU) publishing in the journal Nature demonstrated an effective treatment for hypertrophic cardiomyopathy by using CRISPR technology to edit out the gene responsible for causing the disease from a developing embryo. Hypertrophic cardiomyopathy is a genetic (inheritable) disease that occurs in about two out of every 1,000 people that can result in sudden heart failure and cardiac death. The removal is permanent meaning that subsequent offspring will also be free of the mutation.
Even when carried out soon after fertilization, CRISPR-based editing may produce embryo mosaics where some cells carry the correct edits and other still carry mutant genes. Researchers at OHSU avoided genetically mosaic embryos by injecting the both sperm and oocyte with the repair enzyme prior to fertilization so that all somatic (cells comprising the body body) and germ line cells (cells destined to become oocytes and spermatozoa) derived from subsequent replication and cell division in the embryo after fertilization would be free of the target mutant gene.
For the research conducted at OHSU, scientists worked with healthy donated human oocytes and sperm carrying the genetic mutation that causes cardiomyopathy. Embryos created in vitro (in the laboratory) in this study were not implanted and used only as part of pre-clinical research. Researchers also contend that their editing and repair technique will increase the success of in vitro fertilization (IVF) by creating healthier embryos.
According to scientists the research conducted adhered to scientific and ethical guidelines established by OHSU?s Institutional Review Board was consistent with recommendations made by the National Academy of Sciences and the National Academy of Medicine with regard to human genome editing research. Scientists acknowledge that before moving to clinical trials that additional work needs to be done to refine techniques as well as address broad ethical questions raised by gene editing. In February 2017, representatives from both the National Academy of Sciences and the National Academy of Medicine issued a report recommending that the U.S. government support gene editing research designed to prevent "serious diseases and disability." Sweden and China currently conduct government-supported gene editing research.