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Bibi et al. J Transl Genet Genom 2024;8:119-161 https://dx.doi.org/10.20517/jtgg.2023.50 Page 141

Figure 5. Schematic overview of gene therapy in Prostate cancer. Based on their structural differences, there are currently four types of
nucleases that edit genes in prostate cancer: base editors, zinc-finger nucleases (ZFN), transcription activator-like effector nucleases
(TALENs), and CRISPR-associated nucleases (CRISPR/Cas-9). Viral vectors including adenovirus (Ad), adeno-associated virus (AAV),
herpes simplex virus (HSV), and retroviruses (γ-retroviruses, lentiviruses) play a significant role in the transport of genetic materials.
Genetic materials are introduced through cell membranes via physical methods such as direct injection and chemical methods such as
lipoplex, polyplex, and magnetic nanoparticles. Gene therapies can be classified according to the type of transporter used, which can be
viral and non-viral vectors. These therapies include suicide gene therapy, cytokine gene therapy, tumor suppressor gene therapy,
immunomodulatory gene therapy, gene apoptosis therapy, and corrective gene thera.

the target sequence and the crRNA sequence, the gRNA (guide RNA) unit directs Cas9 to a particular
genomic location . CRISPR/Cas9 technology has been employed to edit genes linked to prostate cancer,
[285]
[280]
including AR, PTEN, TMPRSS2-ERG, BRCA2, and CDK12 .

Transcription activator-like effector nucleases
Transcription activator-like effector nucleases (TALENs) are synthetic nucleases created by fusing the Fok I
endonuclease with a DNA binding domain, resulting in a non-specific nuclease domain that facilitates
targeted cleavage by TALE effectors. The DNA-binding domain consists of a repetitive unit of 33-35
conserved peptides domain with the exception of locations 12 and 13 that are variable and strongly
correlated with particular nucleotide recognition. The DNA cleavage domain of FokI endonuclease is non-
specific. To function as a dimer, the FokI domain requires two constructs with distinct DNA binding
domains for sites in the target genome. Improved activity depends on the quantity of peptides between the
FokI cleavage domain and the TALE DNA-binding domain. TALENs are employed to induce DSBs in
order to initiate DNA repair processes and thus facilitate genome modification [281,286,287] . Prostate cancer
[280]
genes such as AR, PTEN, and PDL1 have been edited using TALENs .

Gene delivery methods
A vector serves as the vehicle used to transfer the desired gene. Gene products can be delivered using viral
vectors, nonviral vectors, as well as chemical and physical vectors [Figure 5]. The selection of appropriate
vectors is an important initial step towards achieving success in gene therapy.