Volume 2, Issue 1, 2026
(Ongoing)
Review Article
Australian Journal of Biomedical Research, 2(1), 2026, aubm012, https://doi.org/10.63946/aubiomed/17736
ABSTRACT:
Background: Sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT) remain major global health burdens. Ex vivo gene-editing therapies aim to achieve durable fetal hemoglobin (HbF) induction or direct mutation correction.
Methods: We systematically reviewed clinical studies of CRISPR-Cas9 or base-editing therapies for SCD and TDT (MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, conference proceedings; 2010–03 December 2025). Eleven studies (>170 treated patients) reporting post-infusion outcomes were included.
Results: All therapies produced robust, pancellular HbF (30–65%) and total hemoglobin in/near the normal range. In TDT (n > 100 evaluable), transfusion independence (≥12 months, Hb ≥9 g/dL) was achieved in 89–100% across platforms, sustained up to >4 years. In SCD (n > 60 evaluable), adjudicated vaso-occlusive crises were eliminated for ≥12 months in ≥97% of patients treated with exagamglogene autotemcel and 100% in smaller cohorts (EDIT-301, BEAM-101). No graft failures occurred. Serious adverse events and one death were attributable to busulfan conditioning, not editing. No therapy-related malignancies or confirmed harmful off-target edits have been reported, although follow-up remains limited (median ~18 months, longest >4 years).
Conclusion: Current evidence from phase 1–3 trials demonstrates that ex vivo gene editing can achieve functional cure for many patients with TDT and severe SCD. Conditioning-related toxicity, limited long-term safety data, and delivery complexity remain critical barriers to broader implementation.
Methods: We systematically reviewed clinical studies of CRISPR-Cas9 or base-editing therapies for SCD and TDT (MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, conference proceedings; 2010–03 December 2025). Eleven studies (>170 treated patients) reporting post-infusion outcomes were included.
Results: All therapies produced robust, pancellular HbF (30–65%) and total hemoglobin in/near the normal range. In TDT (n > 100 evaluable), transfusion independence (≥12 months, Hb ≥9 g/dL) was achieved in 89–100% across platforms, sustained up to >4 years. In SCD (n > 60 evaluable), adjudicated vaso-occlusive crises were eliminated for ≥12 months in ≥97% of patients treated with exagamglogene autotemcel and 100% in smaller cohorts (EDIT-301, BEAM-101). No graft failures occurred. Serious adverse events and one death were attributable to busulfan conditioning, not editing. No therapy-related malignancies or confirmed harmful off-target edits have been reported, although follow-up remains limited (median ~18 months, longest >4 years).
Conclusion: Current evidence from phase 1–3 trials demonstrates that ex vivo gene editing can achieve functional cure for many patients with TDT and severe SCD. Conditioning-related toxicity, limited long-term safety data, and delivery complexity remain critical barriers to broader implementation.
Original Article
Australian Journal of Biomedical Research, 2(1), 2026, aubm013, https://doi.org/10.63946/aubiomed/17744
ABSTRACT:
Lower limb amputation is a major public health challenge that significantly impacts the lives of affected individuals, their relatives, healthcare systems, and society at large. Road traffic accidents (RTAs) are responsible for a significant percentage of the cases of lower limb amputations. The aim of this research is to analyze the existing literature to determine the prevalence of lower limb amputations resulting from severe lower extremity injuries caused by RTAs, as well as to examine the impact that these amputations have on quality of life (QoL) and psychological consequences.
A thorough literature search was carried out across three databases (PubMed, ScienceDirect, and Google Scholar), and a total of six publications were included in this review. The pooled effect was evaluated in Comprehensive Meta-Analysis (CMA) software, employing a random effect model. Based on our analysis, the pooled prevalence of lower limb amputations as a result of RTA was 43.2%. Out of the six studies that were considered for inclusion in this review, only three of them reported on results that were related to psychological outcomes and quality of life. It is necessary to have rehabilitation programs that are all-encompassing and address both the physical and psychological components.
A thorough literature search was carried out across three databases (PubMed, ScienceDirect, and Google Scholar), and a total of six publications were included in this review. The pooled effect was evaluated in Comprehensive Meta-Analysis (CMA) software, employing a random effect model. Based on our analysis, the pooled prevalence of lower limb amputations as a result of RTA was 43.2%. Out of the six studies that were considered for inclusion in this review, only three of them reported on results that were related to psychological outcomes and quality of life. It is necessary to have rehabilitation programs that are all-encompassing and address both the physical and psychological components.