Gene editing changes the base sequence of DNA at a precise, chosen place in the genome. The most widely used tool is CRISPR-Cas9, adapted from a system bacteria use to destroy viral DNA.CRISPR-Cas9 has two parts:
• a guide RNA, designed with a base sequence complementary to the target DNA, which leads the enzyme to the right place
• Cas9, a nuclease that cuts both strands of the DNA at that site.The cell then repairs the break. Simple repair often adds or deletes a few bases, which disrupts the gene and switches it off. If a DNA template with the correct sequence is supplied, the cell can copy it during repair, so a faulty allele is replaced with the correct one. Older tools such as zinc finger nucleases and TALENs work in a similar way but are harder to design.
Gene editing combines well with stem cell therapy. A patient's own stem cells can be removed, edited outside the body to fix the genetic fault, checked, and returned. Stem cells are used because they keep dividing and so provide a lasting supply of corrected cells, and because they are the patient's own they are not rejected. In one approved treatment for sickle cell disease, a patient's bone marrow stem cells are edited so that they make fetal haemoglobin, then returned to the patient.A major risk is cutting at the wrong place. These off-target effects could damage other genes, so edited cells must be carefully screened.
• a guide RNA, designed with a base sequence complementary to the target DNA, which leads the enzyme to the right place
• Cas9, a nuclease that cuts both strands of the DNA at that site.The cell then repairs the break. Simple repair often adds or deletes a few bases, which disrupts the gene and switches it off. If a DNA template with the correct sequence is supplied, the cell can copy it during repair, so a faulty allele is replaced with the correct one. Older tools such as zinc finger nucleases and TALENs work in a similar way but are harder to design.
Gene editing combines well with stem cell therapy. A patient's own stem cells can be removed, edited outside the body to fix the genetic fault, checked, and returned. Stem cells are used because they keep dividing and so provide a lasting supply of corrected cells, and because they are the patient's own they are not rejected. In one approved treatment for sickle cell disease, a patient's bone marrow stem cells are edited so that they make fetal haemoglobin, then returned to the patient.A major risk is cutting at the wrong place. These off-target effects could damage other genes, so edited cells must be carefully screened.