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  • Analytical Review of Novel Gene Therapy and Gene Editing (CRISPR) Approaches in Molecular Targeting of Cancer: Challenges and Future Horizons in Medical Biotechnology”

  • Yasamin Zamani,1,*
    1. Department of Genetics, Faculty of Advanced Science and Technology, Science and Research Branch, Islamic Azad University, Tehran, Iran


  • Introduction: Cancer, as one of the leading causes of global mortality, demands more precise and targeted therapeutic strategies. In recent years, gene therapy and genome editing—particularly CRISPR/Cas technology—have emerged as novel approaches for the molecular targeting of cancer. This review-analytical study first examines the molecular basis of cancer and key genetic targets, including oncogenes, tumor suppressor genes, and DNA repair pathways. Subsequently, it analyzes modern gene therapy approaches, such as gene transfer, gene suppression, genome editing, CRISPR/Cas9 systems, CRISPRa/CRISPRi, base editing, and prime editing. The findings indicate that CRISPR exhibits higher precision, flexibility, and efficiency compared to classical gene therapy methods; however, challenges such as safe delivery, off-target effects, immune responses, and ethical and regulatory considerations remain limiting factors. In conclusion, theintegration of CRISPR with nanocarriers, intelligent delivery systems, and CAR-T cell engineering may open promising horizons in cancer medical biotechnology, provided that safety, ethical, and clinical challenges are addressed.
  • Methods: This study is a systematic review and analytical research designed to comprehensively evaluate novel approaches in gene therapy and gene editing for the molecular targeting of cancer. To gather the required data, a systematic search was conducted across both domestic and international scientific databases. Domestic databases included the Scientific Information Database (SID), Magiran, and Noormags, while international databases comprised PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar. The search strategy utilized a combination of Persian keywords and their English equivalents, including “gene therapy,” “gene editing,” “CRISPR,” “cancer,” “molecular targeting,” “medical biotechnology,” “targeted therapy,” and “nanocarriers.” Boolean operators (AND, OR, NOT) were employed to refine the search and ensure a balance between breadth and precision. The search timeframe was set from 2000 to 2025 to encompass the historical evolution of gene therapy, from first-generationmethods to contemporary genome-editing tools. Inclusion and Exclusion Criteria The inclusion criteria consisted of original research articles, systematic reviews, meta-analyses, clinical trials published in reputable journals, and technical reports from international scientific and health organizations that directly addressed gene therapy, gene editing, or the molecular targeting of cancer. Studies providing sufficient molecular data regarding editing mechanisms, delivery systems, safety profiles, or clinical applications were included. Conversely, exclusion criteria were applied to studies lacking sufficient molecular data, articles published in languages other than Persian or English, promotional or commercial texts, conference abstracts without full-text access, and papers addressing peripheral or irrelevant topics.Screening Process The screening process was conducted in multiple stages. In the first stage, the titles of retrieved articles were reviewed, and irrelevant items were excluded. In the second stage, the abstracts of the remaining articles were screened against the inclusion and exclusion criteria. In the third stage, the full text of articles that passed the abstract screening was retrieved and carefully analyzed. During this phase, articles with insufficient data for analysis or those focusing on tangential topics were excluded. Finally, the selected articles were categorized based on specific thematic axes. These axes included the molecular basis of cancer and genetic targets, gene-editing tools (including Zinc Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), and CRISPR/Cas systems and their derivatives), viral and non-viral delivery systemssafety and off-target toxicity considerations, ethical and regulatory issues, and clinical and pre-clinical applications across various cancer types. Data Analysis Qualitative content analysis was used to analyze the data. In this method, the extracted texts were meticulously read and coded. The initial codes were then categorized into subcategories and main categories based on conceptual similarities. The main categories aligned with the thematic axes mentioned above, while subcategories included specifics such as types of oncogenes, tumor suppressor genes, DNA repair pathways, base editing, prime editing, lipid-based nanoparticles, polymer-based nanoparticles, lentiviral and adenoviral vectors, innate and adaptive immune responses, and ethical challenges associated with human genome editing. Ultimately, theinitial codes were then categorized into subcategories and main categories based on conceptual similarities. The main categories aligned with the thematic axes mentioned above, while subcategories included specifics such as types of oncogenes, tumor suppressor genes, DNA repair pathways, base editing, prime editing, lipid-based nanoparticles, polymer-based nanoparticles, lentiviral and adenoviral vectors, innate and adaptive immune responses, and ethical challenges associated with human genome editing. Ultimately, the findings derived from this analysis were used to address the research questions and provide a comprehensive overview of the current status and future horizons in the molecular targeting of cancer. This methodological approach allowed for a systematic review of the evidence while simultaneously facilitating a critical analysis of current challenges, ambiguities, and research gaps.
  • Results: The findings of this study indicate that gene therapy and gene editing, particularly with the CRISPR system, have shifted the paradigm of cancer treatment from protein-level targeting to genomic and molecular targeting. This shift holds profound implications for medical biotechnology, as it allows for more precise, stable, and multi-layered interventions. However, the same findings suggest that the path toward clinical translation of these technologies remains fraught with serious obstacles, and an overly simplistic view of the future of this field could be misleading. Complexity of Cancer: Cancer at the molecular level is a set of interconnected disorders rather than a collection ofisolated defects. Oncogenes, tumor suppressor genes, DNA repair pathways, immune checkpoints, and signaling pathways are all intertwined in a complex network. This entanglement means that targeting a single point, even with the most precise editing tools, can lead to the activation of compensatory pathways and tumor resistance. Therefore, multi-target and combinatorial approaches are not a luxury, but a strategic necessity. Multiplex CRISPR, which allows for the simultaneous targeting of several genes, is a technical response to this necessity, yet it introduces new challenges such as increased potential for off-target effects, the complexity of guide RNA design, and difficulties in quality control. Evolution of Editing Tools: There has been an evolution in gene editing tools from protein nucleases to RNA-guided systems, and subsequently to base editing andprime editing. This transformation shows that the competitive field in gene editing is not just about efficiency, but also precision and safety. Base editing and prime editing reduce the risk of unwanted mutations and chromosomal breaks by eliminating or reducing double-strand breaks; however, these tools have their own limitations. Base editing is restricted to specific transitions, and prime editing involves more complex design. The main ambiguity is whether a tool can be designed that possesses both the precision of prime editing and the simplicity and efficiency of classic CRISPR, or if we will be forced to choose between the two. Delivery Issues: Delivery is one of the main bottlenecks in the clinical translation of gene editing, and none of the existing systems fulfill all requirements. Viral systems have high efficiency but are accompanied by concerns such as randomintegration, immune responses, and capacity limitations. Non-viral systems have better safety but lower efficiency and poorer tissue-specific targeting. Physical methods are suitable for specific tissues but are invasive and limited to accessible areas. Smart nanocarriers responsive to tumor stimuli are a promising horizon but are still in the preclinical stages; their stability, toxicity, and scalability have not been well evaluated. The core ambiguity is whether a system can be designed that possesses both the efficiency of viral delivery and the safety of non-viral methods, and whether tissue-specific delivery in vivo is possible, or if the ex vivo approach (extracting, editing, and returning cells) will remain the dominant method. Safety: Innate and acquired immune responses against editing components and vectors can reduce therapeutic efficacy and cause dangerous side effects. Off-target toxicity can disrupt vital genes andincrease the risk of secondary carcinogenesis. Mosaicism can lead to disease recurrence from unedited cells. These challenges demonstrate that gene editing, contrary to initial assumptions, is not a purely molecular technology but a complex biological intervention that interacts with the host immune system, tumor dynamics, and genetic heterogeneity. The main question remains whether editing systems can be designed to suppress the immune response without weakening anti-tumor immunity, and whether off-target toxicity can be reduced to zero. Tumor Heterogeneity: A single tumor can contain different genetic sub-clones, some of which are resistant to editing and can cause disease relapse. This heterogeneity limits the efficacy of gene editing and highlights the necessity for combinatorial and multi-target approaches. Organoidmodels and 3D cultures can improve predictions of patient response, but these models cannot yet replicate the full complexity of human tumors. The key ambiguity is whether gene editing can be sufficiently effective in primary human tumors that possess high heterogeneity, or if we will be forced to combine gene editing with immunotherapy and other approaches. Ethical and Regulatory Issues: The editing of embryos and germ cells has raised deep concerns due to the transmission of changes to future generations. Informed consent for treatments with unknown long-term complications is challenging. Justice in access to these expensive technologies raises the risk of them becoming a privilege for wealthy nations. Genetic privacy and the risk of genetic discrimination are also significant concerns. The lack of a bindinginternational regulatory framework increases the potential to evade oversight. The main ambiguity is whether a global consensus can be reached on the permissible boundaries of human genome editing, and whether national legal systems have the capacity to keep pace with the speed of technological progress. Research Gaps: The lack of clinical trials, especially Phase III, is the most significant gap. The absence of standardization in evaluating off-target effects and reporting makes it difficult to compare studies. A lack of long-term studies limits the assessment of the safety and stability of editing. The scarcity of combination studies reduces the possibility of leveraging technological synergies. The deficiency in economic studies makes planning for equitable access difficult, and the lack of ethical studies limits our understanding of the perspectives ofpatients and healthcare providers. The core question is whether these gaps can be closed fast enough for gene editing to become a standard cancer treatment, or if the technology will remain in the preclinical stage.
  • Conclusion: In summary, the findings indicate that CRISPR-based gene editing has drawn promising horizons in medical biotechnology for cancer, but these horizons are conditional upon overcoming technical, safety, ethical, and economic challenges. The path forward includes combining these tools with smart nanocarriers, immunotherapy, in vivo editing, and spatiotemporal control of editing. There is a necessity for more clinical trials, standardization, a global ethical and regulatory framework, and economic studies. It is recommended that future research focus on designing Phase I and II clinical trials with transparent reporting, developing shared criteria for evaluating off-target effects, conducting long-term studies to assess the safety and stability of editing, and performing qualitative studies to understand the perspectives of patients and healthcare providers. Furthermore, it is essential thatinternational ethical and legal frameworks be developed to oversee human genome editing to prevent abuse and inequality in access. Overall, it can be said that gene editing has transformed cancer from an untreatable disease into a manageable, and in some cases, curable disease. However, this transformation is not a sudden event, but a gradual and challenging process. The ultimate success of this technology depends not only on technical advancements but also on interdisciplinary collaboration among molecular biologists, physicians, engineers, ethicists, lawyers, and policymakers. Without this collaboration, there is a risk that gene editing will become a costly, inequitable, and high-risk technology accessible only to a limited group. Therefore, the responsibility of the scientific community and policymakers is to guide this technology toward safe, effective, equitable, and ethicalapplications so that it may truly serve as a medical biotechnology achievement that improves human health.
  • Keywords: Gene Therapy, Gene Editing, CRISPR/Cas9, Cancer, Molecular Targeting

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