In spite of its complicated name, the technique is simple: it consists of forcing the cell machinery to "forget" to read the part of the gene which carries the anomaly. A reading error which sometimes happens spontaneously but can also be provoked, using small elements called oligonucleotides or antisense RNA or a gene (U7) modified to produce antisense RNA.
Before giving rise to a protein, the gene is transcribed into a molecule containing "introns" and "exons". Only the exons used in synthesising the protein. If an exon contains an anomaly, the protein may lose its function. If the exon is "skipped", the protein is modified but in some cases it still remains functional. It all depends on the exon which carries the mutation! This is why this therapy is not suitable for all diseases and, for a single gene, depends on the location of the mutation. It is predictive of the nature of future medicine which will be more than ever based on customized treatment!
The diseases potentially targeted by this technique include Duchenne muscular dystrophy, cystic fibrosis, haemophilia A, beta-thalassemia and viral diseases such as AIDS or herpes.
Stop codon read-through
A "stop codon" is a signal on messenger RNA - an intermediate product between the gene and the protein - which stops the translation of the messenger RNA (mRNA) into protein on the ribosome (protein synthesis).
Sometimes a disease is caused by a mutation which creates a stop codon upstream of its usual position leading to a truncated protein which is not functional. Stop codon read through restores function by allowing the protein synthesis machinery to continue its work as if nothing was wrong.
The diseases potentially targeted by this technique are Duchenne muscular dystrophy and cystic fibrosis.
Recombination via meganucleases
Meganucleases are DNA scissors. They are used for very specific recognition of a unique location in the genome and to induce targeted cutting of the double DNA strand. They are therefore used to cut out an anomaly in a gene.
This operation is combined with the transfer of a DNA-drug. Indeed, when the DNA is cut, it naturally initiates a repair system which will copy the DNA-drug instead of the little part which was cut. It is as simple as that.
The diseases potentially targeted by this technique are all monogenic diseases (recessive or dominant), some viral diseases, some cancers and degenerative diseases.