Correction to “Clinical applications of gene therapy for rare diseases: A review”

Abstract

Papaioannou I, Owen JS and Yáñez-Muñoz RJ. Clinical applications of gene therapy for rare diseases: A review. Int J Exp Pathol 2023 Aug;104(4):154–176. doi: 10.1111/iep.12478. Epub 2023 May 13.

It has been brought to our attention that in paragraph 1 of section 5.3, some details regarding the design of Zolgensma were not accurate. Therefore, the following text was incorrect: “Zolgensma (Onasemnogene Abeparvovec)^196–200 is an AAV-based gene supplementation treatment aimed at directly and permanently restoring SMN1 expression with a single dose. The design of the Zolgensma expression cassette is similar to Luxturna (Figure 5), in using the hybrid CMV–Chicken beta actin promoter to drive the expression of SMN1 cDNA. To enhance expression, the design incorporates an artificial intron (from SV40) and codon optimization. The sequence of AVXS-101 (the vector for Zolgensma) is proprietary and the exact optimizations are not in the public domain, but the effectiveness of this approach was documented by using a similar AAV9 platform.^201–203 A self-complementary design (Figure 12) was employed, where one of the flanking ITRs was a specially engineered variant to synthesize genome dimers, rather than monomers.²⁰⁴”

This should have read: “Zolgensma (Onasemnogene Abeparvovec)^196–200 is an AAV-based gene supplementation treatment aimed at directly and permanently restoring SMN protein production with a single dose. The design of the Zolgensma expression cassette is similar to Luxturna (Figure 5) in using the hybrid CMV–Chicken beta-actin promoter to drive the expression of SMN2 cDNA, and it includes the bovine growth hormone polyadenylation sequence. To enhance expression, the design incorporates an artificial intron (from SV40). Unusually, the sequence of the SMN2 cDNA in Zolgensma was not codon-optimized. The effectiveness of AVXS-101 (the vector for Zolgensma) was corroborated by the work of several other groups using similar self-complementary AAV9-SMN platforms^201–203 (Figure 12), where one of the flanking ITRs was a specially engineered variant to synthesize genome dimers, rather than monomers.²⁰⁴”

We apologize for this error.