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Page 65 Oboma et al. J Transl Genet Genom. 2025;9:62-75 https://dx.doi.org/10.20517/jtgg.2024.74

the cancer cells. Although non-viral vectors are considered safer due to lower immune response risks, a few
challenges in terms of transformation efficiency (how DNA enters cells via lysosomes or nanoparticles) and
[17]
sustained gene expression are often encountered . In prostate cancer, the development of nanoparticles
that can target tumor-specific receptors and deliver therapeutic genes directly to the cancer site is a major
area of ongoing research. Nanoparticles have emerged as a promising tool in gene therapy, offering versatile
and transformative efficient ways of delivering genetic materials into cells. These tiny particles are
engineered to target specific cells or tissues, reducing off-target effects experienced with older tools [18-20] .
Different types of nanoparticles exist in gene therapy: liposome liquid-based nanoparticles, encapsulated
genetic material , polymeric nanoparticles made from biodegradable polymer , and metallic nanoparticles
[l9]
[21]
like gold, silver, and iron oxide . These tools provide several advantages in the field of gene therapy with
[22]
targeted delivery, improved efficiency, and bio-compatibility despite toxicity, immunogenicity, and
[21]
scalability associated with the process .
Gene editing tools
The advent of CRISPR-Cas9 technology has revolutionized gene therapy, enabling precise editing of specific
gene sequences. CRISPR-Cas9 is a tool used to knock out oncogenes or restore the function of tumor
suppressor genes such as PTEN or TP53, which are frequently mutated in advanced prostate cancer . See
[23]
Figure 1. This technology holds significant promise in targeting genetic mutations that lead to resistance to
conventional treatments, such as androgen receptor (AR) mutations that make prostate cancer cells less
responsive to hormone therapy. By directly editing the AR gene, CRISPR-Cas9 could potentially reverse
resistance and enhance the efficacy of existing therapies [24,25] . However, concerns about off-target effects and
the potential for unintended genetic alterations remain a key challenge. Off-target effects include insertion
and deletions of nucleotide at off-target sites, unintended substitution, chromosomal rearrangement
(translocation and inversions), and often mixtures of edited and unedited cells within an individual
(Mosaicism) , as presented in Figure 2.
[25]

Immunogene therapy
Various gene transfer techniques have been explored in prostate cancer therapy, each with its own set of
advantages and challenges. One promising approach is the transfer of tumor suppressor genes such as p53,
which plays a crucial role in regulating cell division and apoptosis. In prostate cancer, the p53 gene is
mutated or inactivated, allowing cancer cells to proliferate uncontrollably . Delivering a functional p53
[26]
gene into prostate cancer cells can restore their ability to undergo programmed cell death, potentially
reducing tumor size and preventing metastasis. Another approach is the use of oncolytic viruses, which are
designed to target, infect, and kill cancer cells while sparing normal cells. These viruses destroy cancer cells
directly and stimulate the immune system to recognize and attack the tumor. Oncolytic virotherapy is a
scientific way of enhancing the body's natural immune response against prostate cancer, particularly in
[27]
combination with other treatments such as checkpoint inhibitors .

Suicide gene
Suicide gene therapy is a promising approach in the treatment of prostate cancer. This technique involves
introducing a gene that makes cancer cells vulnerable to a specific drug, causing them to die . The process
[28]
starts with the introduction of a suicide gene, typically via a viral vector, into the prostate cancer cells. This
gene encodes an enzyme that converts a pro-drug into a toxic compound, selectively killing the cancer cells.
Herpes simplex virus thymidine kinase (HSV-tk): This gene makes cancer cells sensitive to the antiviral
drug ganciclovir, leading to cell death. Cytochrome P450: This gene converts a pro-drug into a toxic
[29]
compound, selectively killing cancer cells . Several clinical trials have investigated the safety and efficacy of
suicide gene therapy for prostate cancer. A study published in 1996 reported the first use of suicide gene
therapy in prostate cancer patients , and numerous studies have demonstrated the potential of this
[30]