Cervical cancer represents one of the most important malignancies among women worldwide. Current therapeutic approaches for cervical cancer are reported not only to be inadequate for metastatic cervical cancer, but are also considered as cytotoxic for several patients leading to serious side effects, which can have negative implications on the quality of life of women. Therefore, there is an urgent need for the development of innovative and effective treatment options. Oncolytic viruses can eventually become effective biological agents, since they preferentially infect and kill cancer cells, while leaving the normal tissue unaffected. Moreover, they are also able to leverage the host immune system response to limit tumor growth. This review aims to systematically describe and discuss the different types of oncolytic viruses generated for targeting cervical cancer cells, as well as the outcome of the combination of virotherapy with conventional therapies. Although many preclinical studies have evaluated the therapeutic efficacy of oncolytic viruses in cervical cancer, the number of clinical trials so far is limited, while their oncolytic properties are currently being tested in clinical trials for the treatment of other malignancies.

Despite the major advances in screening and therapeutic approaches, gynaecological malignancies still present as a leading cause of death among women of reproductive age. Cervical cancer, although largely preventable through vaccination and regular screening, remains the fourth most common and most lethal cancer type in women, while the available treatment schemes still pose a fertility threat. Ovarian cancer is associated with high morbidity rates, primarily due to lack of symptoms and high relapse rates following treatment, whereas endometrial cancer, although usually curable by surgery, it still represents a therapeutic problem. On the other hand, benign abnormalities, such as fibroids, endometriosis, placental, and embryo implantation disorders, although not life-threatening, significantly affect women’s life and fertility and have high socio-economic impacts. In the last decade, targeted gene therapy approaches toward both malignant and benign gynaecological abnormalities have led to promising results, setting the ground for successful clinical trials. The above therapeutic strategies employ both viral and non-viral systems for mutation compensation, suicide gene therapy, oncolytic virotherapy, antiangiogenesis and immunopotentiation. This review discusses all the major advances in gene therapy of gynaecological disorders and highlights the novel and potentially therapeutic perspectives associated with such an approach.

We have previously demonstrated that both the original γ-globin lentiviral vector (LV) GGHI and the optimized GGHI-mB-3D LV, carrying the novel regulatory elements of the 3D HPFH-1 enhancer and the 3’ β-globin UTR, can significantly increase HbF production in thalassemic CD34⁺ cells and ameliorate the disease phenotype in vitro. In the present study, we investigated whether the GGHI-mB-3D vector can also exhibit an equally therapeutic effect, following the transduction of sickle cell disease (SCD) CD34⁺ cells at MOI 100, leading to HbF increase coupled with HbS decrease, and thus, to phenotype improvement in vitro. We show that GGHI-mB-3D LV can lead to high and potentially therapeutic HbF levels, reaching a mean 2-fold increase to a mean value of VCN/cell of 1.0 and a mean transduction efficiency of 55%. Furthermore, this increase was accompanied by a significant 1.6-fold HbS decrease, a beneficial therapeutic feature for SCD. In summary, our data demonstrate the efficacy of the optimized γ-globin lentiviral vector to improve the SCD phenotype in vitro, and highlights its potential use in future clinical SCD trials.

Over recent years, epitranscriptomic research has provided a new layer of gene regulation during hematopoietic development and aberrant hematopoiesis. Among the 170 identified RNA chemical marks, N⁶-methyladenosine (m⁶A) is the most abundant in eukaryotic cells and plays a critical role in various biological processes. This dynamic modification is regulated by a series of methyltransferases, demethylases, and m⁶A binding proteins, known as writers, erasers, and readers, respectively. Emerging evidence suggests that m⁶A modification and its regulators are involved in every aspect of normal hematopoietic development, from the emergence of hematopoietic stem cells to the generation of mature blood cells. Also, it has been established that abnormal expression of m⁶A regulators is implicated in the initiation of blood diseases. In this review, we summarize the latest findings regarding the role of m⁶A in erythropoiesis and highlight its implications in the pathophysiology of hemoglobin disorders.

β-thalassemia is characterized by reduced or absence ofβ-globin production, resulting in anemia. Current therapies include blood transfusion combined with iron chelation. BM transplantation, although curative, is restricted by the matched donor limitation. Gene therapy, on the other hand, is promising, and its success lies primarily on designing efficient globin vectors that can effectively and stably transduce HSCs. The major breakthrough inβ-thalassemia gene therapy occurred a decade ago with the development of globin LVs. Since then, researchers focused on designing efficient and safe vectors, which can successfully deliver the therapeutic transgene, demonstrating no insertional mutagenesis. Furthermore, as human HSCs have intrinsic barriers to HIV-1 infection, attention is drawn towards theirex vivomanipulation, aiming to achieve higher yield of genetically modified HSCs. This paper presents the current status of gene therapy forβ-thalassemia, its success and limitations, and the novel promising strategies available involving the therapeutic role of HSCs.

Over recent years, epitranscriptomic research has provided a new layer of gene regulation during hematopoietic development and aberrant hematopoiesis. Among the 170 identified RNA chemical marks, N6-methyladenosine (m6A) is the most abundant in eukaryotic cells and plays a critical role in various biological processes. This dynamic modification is regulated by a series of methyltransferases, demethylases and m6A binding proteins, known as writers, erasers and readers, respectively. Emerging evidence suggests that m6A modification and its regulators are involved in every aspect of normal hematopoietic development, from the emergence of hematopoietic stem cell to the generation of mature blood cells. Also, it has been established that abnormal expression of m6A regulators is implicated in the initiation of blood diseases. In this review, we summarize the latest findings refarding the role of m6A in erythropoiesis and highlight its implication in the pathophysiology of hemoglobin disorders.