Gene therapy and gene correction: targets, progress, and challenges for treating human diseases

Current and Future Treatments for Classic Galactosemia

“…Gene therapy and gene correction techniques aim to permanently compensate for the primary genetic defect [49,50]. In conventional gene therapy, this is achieved by providing patients with the correct coding DNA (cDNA) sequence of the defective gene leading to the expression of normal protein [50,51].…”

“…In conventional gene therapy, this is achieved by providing patients with the correct coding DNA (cDNA) sequence of the defective gene leading to the expression of normal protein [50,51]. Delivery is accomplished by the use of vectors, either viral or non-viral, containing the genetic sequence of the protein [49,52,53]. In recent decades, significant advances have been made and gene therapy is showing great promise in animal models and clinical trials of inborn errors of metabolism [51][52][53].…”

“…Important future challenges will be focused at safety and efficacy. Safety concerns encompass elicited immune responses by the viral vector capsid proteins and the transgene product, and possible off target effects leading to insertional mutagenesis as well as genomic instability [49,52]. With regard to efficacy, Rasmussen et al reported differences between liver and brain transgene activity.…”

Repurposing elesclomol, an investigational drug for the treatment of copper metabolism disorders

“…However, unlike small molecules like elesclomol, which can correct copper deficiency throughout the body, the proposed gene therapy approach is limited to the brain, leaving other tissues uncorrected. While there is significant therapeutic potential, gene therapy approaches still present several challenges with regards to gene delivery, safety, efficacy, and costs before they become more common in clinical use [24].…”

A brief review of reporter gene imaging in oncolytic virotherapy and gene therapy

“…Engineered viruses have emerged as the workhorses of oncolytic virotherapy (OV) and gene therapy. 1 , 2 , 3 , 4 To date, one herpes simplex-derived oncolytic virus (Imlygic), three adeno-associated virus (AAV) gene therapies (Glybera, Luxturna, and Zolgensma) and five retro- or lentiviral cellular gene therapies (Strimvelis, Kymriah, Tecartus, Yescarta, and Zynteglo) have gained marketing approval in the United States and/or the European Union. Ongoing clinical development of viral vectors for other disease indications is expected to benefit greatly from incorporating reporter gene imaging (RGI) to shorten development timelines by providing critical information on the biodistribution, magnitude, and duration of viral gene expression.…”