| abstract |
A recombinant adeno-associated virus (rAV) vector presenting an expression cassette comprising a modified human low-density lipoprotein receptor (RLBDh) gene, in which said RLBDh gene encodes a modified RLBDh that is resistant to degradation of RLBDh by interfering with the PCSK9 pathway and the DIRL pathway, and is capable of reducing cholesterol after expression in a subject, in which the RLBDh presents 95% identity to 99.9% identity with a sequence selected from among the SEQ ID NO: 1 and 3-7, and in which said modified RLBDh comprises: (a) one or more substitutions of an amino acid selected from: N295D, H306G, V307D, N309A, D310N, L318H or L318D, based on the numbering of SEQ ID NO: 1; and (b) an amino acid substitution of at least one of L769R, K809R or C818A, based on the numbering of SEQ ID NO: 1. |