Gene therapy as a potential tool for treating neuroblastoma—a focused review

Abstract

Neuroblastoma, a solid tumor caused by rapid division of undifferentiated neuroblasts, is the most common childhood malignancy affecting children aged <5 years. Several approaches and strategies developed and tested to cure neuroblastoma have met with limited success due to different reasons. Many oncogenes are deregulated during the onset and development of neuroblastoma and thus offer an opportunity to circumvent this disease if the expression of these genes is restored to normalcy. Gene therapy is a powerful tool with the potential to inhibit the deleterious effects of oncogenes by inserting corrected/normal genes into the genome. Both viral and non-viral vector-based gene therapies have been developed and adopted to deliver the target genes into neuroblastoma cells. These attempts have given hope to bringing in a new regime of treatment against neuroblastoma. A few gene-therapy-based treatment strategies have been tested in limited clinical trials yielding some positive results. This mini review is an attempt to provide an overview of the available options of gene therapy to treat neuroblastoma.

Biodegradable Gene Carriers Containing Rigid Aromatic Linkage with Enhanced DNA Binding and Cell Uptake

“…In recent decades, gene therapy has been regarded as a promising strategy to cure multiple inherited and infectious diseases [1,2,3,4,5]. Due to the numerous obstacles during gene delivery—such as gene packing, cellular uptake, endosomal escapem and translocation into the nucleus [6]—successful gene transfection requires appropriate gene vectors.…”

Evaluation and Optimization of Poly-d-Lysine as a Non-Natural Cationic Polypeptide for Gene Transfer in Neuroblastoma Cells

“…Furthermore, we evaluated its stability against proteases as its effects on cell viability. We selected neuroblastoma cells since this cancer is the most common malignant tumor found in infancy [ 37 , 38 ] and has a survival rate of less than 20% [ 39 ]. Neuroblastoma treatments are based mainly on surgery, chemotherapy, and radiotherapy, but because of the nature of the disease, it can metastasize into other tissues with ease [ 38 ]; therefore, recovery rates are generally low [ 40 ].…”

“…Furthermore, frequent complications of these treatments include high levels of drug toxicity and low specificity on the target tissue, as well as the adaptability of the tumor cells to the drugs used, leading to what is known as refractory cancer [ 41 ]. Consequently, it is imperative to discover alternative treatments, and gene therapy has been proposed as a potential tool for treating this tumor [ 39 ]. We tested several DNA–PDL complexes and show that PDL has a high transfection efficiency in the SH-SY5Y neuroblastoma cell line when compared to HeLa and 3T3 cell lines.…”

Long-Term Efficacy and Safety of Insulin and Glucokinase Gene Therapy for Diabetes: 8-Year Follow-Up in Dogs

“…Indeed, in 2012, Glybera by UniQure, a muscle-directed, adeno-associated viral (AAV) vector-based gene therapy for the treatment of lipoprotein lipase deficiency, became the first gene therapy product of the western world to gain market approval in Europe 2, 3. Having overcome many of the challenges that hampered the success of gene therapy in the initial years, the technology has broadened its range of potential applications from monogenic to non-hereditary, complex diseases, such as cancer, cardiovascular disease, and diabetes 1, 4, 5, 6…”