Early successes using CRISPR technique are promising
Q: I read that CRISPR is a treatment now, and I remember an article you wrote about it a while ago. Please give an update.
A: The 3-plus billion nucleic acid base pairs of human DNA, coded on 46 chromosomes, are the hereditary map that encodes production and control of 20,000-plus necessary proteins. Many genetic mutations in these base pairs that contribute to the development of certain diseases have been identified.
CRISPR/Cas 9 (CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats and is pronounced "crisper"):
• Is part of many bacterias' defense against attacks from viruses. When a bacterium kills an invading virus, it slices and scoops up the remains of that virus's genetic code, "memorizing" this information by storing it in its own genome. If/when the same type of virus later attacks, this bacterium uses this stored information to produce a protective virus-specific enzyme (called Cas9) designed to destroy the virus' specific sequence of base pairs. We have learned how to utilize this mechanism to cause the creation of Cas9 enzymes specific for any desired genetic sequence (rather than against an attacking virus).
• Can be utilized to cut out a desired genetic sequence from a strand of DNA; for example, to cut out a gene that has an erroneous base pair. If the disease in question is treatable by simply cutting out the erroneous genetic sequence, this step alone can be a treatment.
• Can insert a desired genetic sequence (for example, the correct genetic code for a desired protein) exactly where the defective genetic sequence was removed, utilizing the inherent command and control mechanisms for that protein.
From this description, it should be evident that CRISPR has amazing potential to treat many diseases:
• Simply cutting out undesired genetic sequences can be a treatment, such as for HIV which inserts itself into a patient's genome. This technique could also be used to directly attack an infecting organism (viral/bacterial/other), similar to what antibiotics do.
• Cutting out an incorrect genetic sequence and inserting a correct sequence could potentially treat many genetic disorders.
• For example, sickle cell disease (SCD) is caused by a mutation causing the sixth codon of the hemoglobin beta-chain gene to have thymine instead of adenine. Removing this incorrect sequence and replacing it with the correct sequence in the patient's bone marrow cells could possibly cure a patient's SCD. A recent publication highlighted a patient treated with CRISPR for SCD, noting that one year later she is symptom-free with genetically corrected red cells still multiplying in her bone marrow.
• A patient treated in Germany with CRISPR for a different hemoglobin disease, beta-thalassemia, also continues to do well, not having needed a blood transfusion in more than 15 months.
There are many other possible medical uses of CRISPR.
There are concerns:
• What if the genetic sequence cut out is not (only) the desired one, or if the inserted new sequence is not placed correctly (inserted in the wrong place or with the wrong code); might the patient develop cancer or some other condition?
• Are there ethical concerns (might these techniques be used to create "designer' babies")? Are there other potential abuses as well?
• If this technology is used to modify insects, might the disruption of the food chain have unintended consequences?
The early successes described above are quite encouraging, and many more trials using CRISPR in more patients and for other diseases have started or will soon begin. For example, Duke University researchers have been treating mice with a variant of Duchenne muscular dystrophy with CRISPR-altered cells, and although there have been some immune responses and alternative genes edited in their mouse subjects, there is also reason for encouragement with their results.
Jeff Hersh, Ph.D., M.D., can be reached at DrHersh@juno.com