Orphan diseases are rare and often life-threatening diseases that typically do not have an effective treatment. Patients and families hope for treatments to over 6,000 Orphan Diseases, but in the meantime, they wait and suffer. The need for effective Orphan Disease treatments is real and urgent.

Tremendous scientific and technical progress has been made toward the ultimate goal of correcting inborn errors in genes. The Nobel Prize in Physiology or Medicine in 2006 was awarded for RNA interference (RNAi), which has validated many techniques for oligonucleotide-based therapies. In 2007, the Nobel Prize was awarded for Gene Targeting, which encompasses the underlying science for transferring genes into the genome. TGA takes advantage of the techniques and science inherent in these discoveries in order to target and correct the gene itself.

Targeted Gene Alteration was developed to correct inborn single point mutations in genes. TGA utilizes single-strand oligonucleotides that exploit the innate DNA repair machinery in the nucleus of the cell (see animation). The TGA oligonucleotide (blue) enters the cell and binds to the complementary sequence around the mutation (red), except for a mismatch at the mutation site. Endogenous DNA repair enzymes resolve this mismatch to correct the mutation. Cells that are repaired with TGA can subsequently grow and divide with normal transcription and regulation.