The advancement of gene therapy has elicited enthusiasm throughout various scien­tic elds and society as a whole. Progress in both fundamental and clinical research has played a crucial role in propelling and directing this inventive and imaginative endeavor. The rst uses of gene therapy were mostly centered on addressing genetic illnesses of a simpler kind, including severe combined immunodeciency [1]. In these cases, the primary objective was frequently to substitute the defective gene responsible for the ailment [2]. Nevertheless, the emergence of cancer gene therapy has brought out novel concepts and methodologies, supported by the understanding that cancer originates from genetic changes occurring in both germline and somatic cells [3]. Gene treatments have shown promise in the therapy of prostate cancer due to their ability to diagnose early stage PCa via a blood test for prostate-specic antigen (PSA) and their potential to target primary prostate cancer lesions by intra­prostatic injection [4]. The capacity to precisely guide intraprostatic administration of gene therapy carriers is of great use for the implementation of immunotherapy­based gene therapy and cytotoxic strategies. Furthermore, because of the often slow-growing nature of prostate cancer, there has been a signicant emphasis on developing non-aggressive therapy options for individuals with early stage and localized illnesses [5]. This objective has been and continues to be of utmost impor­tance. The initiation of the rst clinical trial for in situ gene therapy in PCa in 1999, as well as subsequent studies, was a result of clinical and preclinical investigations that focused on the unique features of PCa and advancements in cancer gene ther­apy [6, 7]. These studies laid the groundwork for the implementation of this clinical strategy. The introduction of gene therapy in the salvage context after initial radia­tion was a result of advancements in the improvement of novel ways for PCa ther­apy [6, 7]. In addition, the rst advancements in gene therapy for PCa prompted the emergence of novel gene delivery methods using viral vectors and liposomes, alongside the creation of innovative preclinical models for evaluating these advance­ments [8]. These early investigations also contributed to an enhanced comprehen­sion of the bystander impact of immunostimulatory genes and cytotoxic transfer into PCa tissues [9]. The fundamental comprehension of the bystander consequence has inuenced the examination of interactions between PCa and the tumor microen­vironment. This topic is now being extensively explored based on the idea of sys­temic immuno-oncology and cytotoxic combination treatment regimens [10–12]. While the implementation of gene therapy for PCa in clinical settings has not pro­gressed as rapidly as it has for hematological malignancies, there have been notable advancements in PCa imaging techniques that are bringing gene therapy functions closer to clinical use [2].

Viruses have undergone evolutionary changes that enable them to effectively invade certain cells and facilitate the delivery of genetic materials, leading to the translation and transcription of viral proteins. Therefore, they provide a prospective approach for gene delivery [17]. The process of genetically modifying viral genomes allows for the alteration of viral infectivity, as well as the corresponding immunological response of the host, and facilitates the targeted delivery of certain genes to specic cells [18]. A variety of viruses have been chosen for use as possible vectors in the eld of gene therapy, including those specically targeted for PCa gene therapy. Adenoviruses, retroviruses, and adeno-associated virus (AAV) are often investi­gated as vectors for gene therapy in PCa. Each of these vectors has distinct benets, drawbacks, and variations in connection with their replication competency [19].