Evidence ratings are used to describe "closeness to the current project" and are not a substitute for journal impact factors. High-impact literature can increase credibility, but only if the species, strain, capsid, expression cassette, route of administration, dose, and endpoint are close enough to serve as a direct basis for design.
|
Level |
Definition |
Recommended usage |
|
A |
Same species/strain, same tissue cells, same pathway, and have quantitative and functional endpoints |
Can be used as the core basis for the main plan and dosage interval |
|
B |
Same species and target tissue, but one difference in capsid, expression cassette or pathway |
Supports candidate sorting, still needs pre-experimentation |
|
C |
Different species or similar only at the organizational level |
Used to propose hypotheses, not to promise to reproduce |
|
D |
In vitro, single reporter gene, supplier information or no complete method |
For clues only, independent verification is required |
Clinical success demonstrates the feasibility of the AAV platform, but it cannot replace the dosage and safety verification of research-grade vectors in specific models. High-quality clinical studies of the eye, liver, and muscle/nervous system can be used in the risk framework; specific experiments should still be based on evidence from the same model. [16-1 to 16-4]
References for this chapter
[16-1] Mendell JR, et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med. 2017;377:1713-1722. DOI:10.1056/NEJMoa1706198. PMID:29091557. [H]
[16-2] Russell S, et al. Voretigene neparvovec phase 3 trial. Lancet. 2017;390:849-860. DOI:10.1016/S0140-6736(17)31868-8. [H]
[16-3] Pipe SW, et al. Gene therapy with etranacogene dezaparvovec for hemophilia B. N Engl J Med. 2023;388:706-718. DOI:10.1056/NEJMoa2211644. [N/H]
[16-4] Lv J, et al. AAV1-hOTOF gene therapy for autosomal recessive deafness 9. Lancet. 2024;403:2317-2325. DOI:10.1016/S0140-6736(23)02874-X. PMID:38280389. [N]