NKG-001, a new generation gene therapy being tested in SMA

NKG-001, a novel gene therapy product featuring a next-generation AAV« adeno-associated virus » , ou virus adéno-associé est un petit virus à ADN simple brin. Il fait partie de la famille des Parvoviridae et appartient au genre des Dependovirus. La particule virale est constituée d’un brin d’ADN de polarité positive ou négative protégé par une capside. La taille moyenne d’une particule d’AAV et de 18 à 22 nm. Les AAV sont les seuls parvovirus non autonomes. Lorsqu’on emploie « rAAV » , il s’agit du virus AAV recombinant, c’est-à-dire qu’il a été modifié pour devenir un vecteur (et n’est donc plus virulent). vector (cceAAV for covalently closed-end double-stranded AAV), was tested intravenously in two children with proximal spinal muscular atrophy (SMA) aged one year (with two copies of SMN2) and two years (with three copies of SMN2) who were already being treated with nusinersen or risdiplam.

• NKG-001 shares the same genetic sequence as that used for Zolgensma, except at the terminal level (mITR is replaced by TeIN) in order to increase the efficiency of transduction and also the expression of the transgene.
• It was well tolerated, with no serious side effects.
• Both children showed rapid improvements in motor function.

Gene therapy with covalently closed-end AAV vector for spinal muscular atrophy. Duan H, Zhang C, Zhang Z et al. Mol Ther. 2025 Jun.