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Page 142 Bibi et al. J Transl Genet Genom 2024;8:119-161 https://dx.doi.org/10.20517/jtgg.2023.50

Viral vectors for gene delivery
The first popular vectors for gene delivery to specific tissues were viruses. Viral surface proteins interact
with host receptors to trigger endocytosis. Upon entry, viruses discharge their genome into the nucleus to
facilitate gene expression. The most significant viral vectors include adenovirus (Ad), adeno-associated
virus (AAV), herpes simplex virus (HSV), and retroviruses (γ-retroviruses, lentiviruses) [288-290] .

Nonviral vectors
Biocompatible materials such as lipid molecules, naked DNA, chromosomes, plasmids, and conjugate
complexes, along with positively charged molecules, are less likely to induce immune responses in the body
compared to nonviral vectors or delivery methods for gene therapy . Genetic materials are introduced
[284]
through cell membranes via a physical process known as nonviral gene delivery. Neon injection, ballistic
DNA injection, sonoporation, photoporation, magnetofection, and hydroporation are examples of physical
gene delivery techniques. The direct infusion of genomic content using a needle is referred to as needle
injection. Magnetofection is the process of concentrating DNA or RNA into target cells with the assistance
of magnetic molecules . Magnetic nanoparticles are nanosized particles that are susceptible to external
[291]
magnetic fields and possess magnetic characteristics. By attaching magnetic nanoparticles to gene carriers
(plasmids, siRNA, CRISPR/Cas9, or miRNA) and using a magnetic field to guide them to the tumor site,
therapeutic genes can be delivered into the target cells. Because magnetic nanoparticles can pass through
some of the obstacles in the TME - such as the extracellular matrix, blood flow, and interstitial pressure -
[292]
they can enhance the efficiency and specificity of gene transport .

Gene therapy for prostate cancer treatment
Cancer arises when the regular processes of cell growth and programmed cell death, known as apoptosis,
are disturbed. Advancements in cancer therapy require innovative drugs with unique mechanisms of action,
multiple methods of inducing cell death, and compatibility with existing treatments. These criteria are also
[269]
applicable to gene-based treatments, representing a promising avenue for advancing cancer therapy .

Gene therapy studies using viral vectors
Several gene therapy strategies employing viral vectors, such as suicide gene therapy involving the addition
of genes that alter enzymes and chemical molecules to generate harmful compounds, cytokine gene therapy,
and tumor suppressor gene therapy, are being developed or under investigation for the management of
prostate cancer [Figure 5] (as following explained in 9th section).
[269]

Gene therapy studies using nonviral vectors
Prostate cancer treatment employs diverse gene therapy methods, including gene apoptosis therapy that
substitutes the altered gene with one that regulates the death of cancer cells. Corrective gene therapy utilizes
tumor suppressor genes to regain regular cell developmental growth, while immunomodulatory gene
therapy activates the immune system with specific genes. Additionally, suicide gene therapy introduces
genes that cause alterations in chemical compounds or enzymes, forming toxic substances. These strategies
represent the varied approaches used in prostate cancer gene therapy [Figure 5]. In addition, by
[293]
employing targeting ligands that can identify certain receptors in the target tissue, the targeting capacity of
[293]
nonviral vectors can be increased , as explained in the following 9th section.

POSSIBILITY OF SUCCESS OF GENE THERAPY IN PROSTATE CANCER
Numerous variables, including the virus type, delivery method, dosage, target tissue, immune response, and
possible side effects, affect the safety and effectiveness of viral vectors. Regarding transfection efficiency,
stability, specificity, immunogenicity, toxicity, and insertional mutagenesis, various viral vectors have