• Ethan Cottrill, Zach Pennington, Nathan Sattah, Crystal Jing, Dave Salven, Eli Johnson, Max Downey, Shyni Varghese, Brett Rocos, and William Richardson.
• Department of Orthopaedic Surgery, Duke University Health System, Durham, NC, USA; Department of Biomedical Engineering, Duke University, Durham, NC, USA. Electronic address: ethan.cottrill@duke.edu.
• World Neurosurg. 2024 Jun 1; 186: 219234.e4219-234.e4.

ObjectiveTo analyze the extant literature describing the application of gene therapy to spinal fusion.MethodsA systematic review of the English-language literature was performed. The search query was designed to include all published studies examining gene therapy approaches to promote spinal fusion. Approaches were classified as ex vivo (delivery of genetically modified cells) or in vivo (delivery of growth factors via vectors). The primary endpoint was fusion rate. Random effects meta-analyses were performed to calculate the overall odds ratio (OR) of fusion using a gene therapy approach and overall fusion rate. Subgroup analyses of fusion rate were also performed for each gene therapy approach.ResultsOf 1179 results, 35 articles met criteria for inclusion (all preclinical), of which 26 utilized ex vivo approaches and 9 utilized in vivo approaches. Twenty-seven articles (431 animals) were included in the meta-analysis. Gene therapy use was associated with significantly higher fusion rates (OR 77; 95% confidence interval {CI}: [31, 192]; P < 0.001); ex vivo strategies had a greater effect (OR 136) relative to in vivo strategies (OR 18) (P = 0.017). The overall fusion rate using a gene therapy approach was 80% (95% CI: [62%, 93%]; P < 0.001); overall fusion rates were significantly higher in subjects treated with ex vivo compared to in vivo strategies (90% vs. 42%; P = 0.011). For both ex vivo and in vivo approaches, the effect of gene therapy on fusion was independent of animal model.ConclusionsGene therapy may augment spinal fusion; however, future investigation in clinical populations is necessary.Copyright © 2024 Elsevier Inc. All rights reserved.

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