Gene therapy

The optimal solution for recessive retinal dystrophies

The end goal of gene therapy is to provide diseased cells with cDNA corresponding to a non-mutated targeted gene. To achieve this goal, HORAMA uses vectors, which penetrate the target cells and transfer cDNA into the nucleus (a process termed transduction). Once there, the non-mutated gene can then produce the functional protein it encodes. These vectors are generally viruses stripped of their infectious or viral activity. To develop these vectors, HORAMA uses recombinant-adeno-associated viruses (rAAV), the first-in-class vectors in the gene therapy race.

HORAMA rAAV vector technology is designed for one-time administration to produce a longterm therapeutic protein.

HORAMA target diseases are monogenic retinal dystrophies, which have a progressive disease course. rAAV technology is safe and well tolerated, as demonstrated in several clinical studies conducted in recent years, including the Phase I/II clinical study of RPE65-linked retinal dystrophy led by the scientific founders of HORAMA.


The retina is particularly amenable to gene therapy

The target cells, photoreceptors and retinal pigment epithelium (RPE) cells, can be transduced by subretinal injection.

The retina is small and enclosed, allowing localised delivery of a relatively modest amount of gene therapy vector at or near the target site.

The eye attempts to limit local immune and inflammatory responses to preserve vision. This phenomenon, known as ocular immune privilege, is primarily mediated mainly by the blood-retina barrier, and involves a combination of local and systemic mechanisms.

Moreover, the high stability of the targeted retinal cell populations and the lack of cell division allows the use of non-integrating vector systems such as rAAVs, thus reducing the possibility of malignant transformation of the target cells (insertional mutagenesis and oncogenesis), which can occur following insertion of the vector genome into that of the host cell.