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Gene & Protein in Disease Enhancing fertility with CRISPR

gene function in brain development. Advancements in poised to revolutionize research in reproductive biology,
CRISPR technology precision and effectiveness have with potential breakthroughs in germplasm preservation,
ushered in a new era of genome editing capabilities. the generation of artificial gametes and gonads from
Co-delivery of Cas9 mRNA and sgRNA offers an efficient stem cells, and further investigations into reproductive
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strategy, especially for editing non-dividing cells, with microbiomes. The realization of CRISPR’s full potential
a focus on minimizing safety concerns. Addressing the in editing germlines, gametes, and gametic precursors
challenge of co-delivering RNA molecules with distinct to benefit the human community relies on overcoming
sizes, Abbasi et al. utilized a PEGylated polyplex micelle challenges such as off-target mutations, mosaicism, and
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(PM) to encapsulate both Cas9 mRNA and sgRNA, ethical considerations. Ongoing enhancements in CRISPR
demonstrating widespread genome editing across various systems, including the refinement of Cas9 enzymes,
parenchymal cells in the mouse brain. Similarly, Chen improved gRNA design, utilization of smaller nucleases,
et al. reviewed the potential of synthetic carriers for nanoparticle-based delivery techniques, and exploration
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achieving tissue-selective gene editing by co-delivering of anti-CRISPR proteins, contribute to increasing efficacy
Cas9 mRNA and sgRNA targeting PCSK9 using selective and specificity. With continued research and judicious
organ-targeting lipid nanoparticles (LNPs). regulation, CRISPR technology holds the promise
of significantly impacting reproductive health and
Researchers have tackled the delivery challenge of
Cas9 ribonucleoprotein (Cas9 protein plus sgRNA), contributing to the well-being of individuals and future
generations.
which arises from the large size of Cas9 and the negative
charge of sgRNA. Wei et al. developed lung-targeting Addressing ethical and safety concerns associated with
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5A2-DOT-50 LNPs, achieving tissue-specific gene editing the modification of CRISPR technology requires responsible
in the livers and lungs of mice with high efficiency. Kai usage and management in reproductive applications.
et al. engineered a thermostable GeoCas9 variant Striking a balance between moral considerations and
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for robust genome editing, demonstrating significant scientific advancements is essential. Comprehensive
editing efficiency in the liver and lungs of mice. Shen legislation must be enacted to address safety, social, and
et al. constructed traceable nano-biohybrid complexes ethical issues, ensuring careful navigation of potential
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(F-TBIO) for efficient delivery of CRISPR/Cas9 plasmids pitfalls. To minimize unexpected outcomes, efforts should
into brain lesions, successfully knocking out the Bace1 gene be directed toward enhancing the precision and accuracy
in mice with Alzheimer’s disease. Lee et al. 132,133 developed of CRISPR systems. Through fostering a collaborative and
CRISPR-Gold, a gold nanoparticle-based system for interdisciplinary approach, we can harness the benefits of
CRISPR delivery, demonstrating superior HDR efficiency, CRISPR while upholding moral standards, safeguarding
lower toxicity, and potential therapeutic applications individual welfare, and ensuring the well-being of present
across various contexts. and future generations.
In summary, these strategies represent promising Acknowledgments
advancements in targeted Cas9 delivery using various
systems, opening new avenues for enhanced genome All the figures were drawn using Biorender.com.
editing. Future research may focus on refining delivery Funding
strategies, particularly for therapeutic applications, with a
notable emphasis on reproductive systems. None.

7. Conclusion and future prospectives Conflict of interest
The discovery of CRISPR technology presents significant The authors declare that they have no competing interests.
potential for revolutionizing reproductive biology and
addressing a broad spectrum of genetic and reproductive Author contributions
issues. This technology opens up novel avenues for treating Conceptualization: Ali Afzal, Muhammad Babar Khawar
gynecological tumors, reversing deleterious genetic Supervision: Xinying Ji, Muhammad Babar Khawar
changes, and advancing contraceptive development. Visualization: Umair Ali Khan Saddozai, Muhammad
Nonetheless, it is crucial to conscientiously address Babar Khawar
and regulate ethical concerns, encompassing the risks Writing – original draft: Shiza Hanif, Hamid Nawaz,
of unforeseen mutations, the ramifications of germline Muhammad Babar Khawar
editing, and the ethical considerations surrounding Writing – review & editing: Ali Afzal, Muhammad Babar
eugenics and designer babies. CRISPR technology is Khawar

Volume 3 Issue 1 (2024) 10 https://doi.org/10.36922/gpd.2701