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Gene & Protein in Disease Enhancing fertility with CRISPR

crucial for harnessing the full potential of CRISPR to modify and efficacy considerations before widespread clinical
genomes according to desired outcomes. Furthermore, applications.
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it has been shown that the CRISPR/Cas system can
induce mutations in mature oocytes during meiosis, 3.3. Gene editing for assisted reproduction
offering a potential avenue to alter specific fertility-related techniques
genes or prevent genetic defects in children. However, ARTs represent medical procedures primarily employed to
58
ethical concerns, along with biological and physiological address reproductive disorders in individuals, facilitating
considerations, have led most scientists to declare CRISPR the conception of babies. Examples of these techniques
editing of germline genomes as currently unethical on include donor insemination, egg donation, intracytoplasmic
clinical scales. Nevertheless, research activities persist, sperm injection (ICSI), and in vitro fertilization (IVF). 69-71
aiming to find safe and sound solutions to overcome these The increasing prevalence of these technologies has raised
hurdles. 59 concerns about their safety, with reported complications
such as low birth weight, preeclampsia, limited epigenetic
3.2. Gene editing in embryos
variability, compromised embryonic quality, and stress. 72,73
The application of CRISPR on human embryos holds the
potential to completely eliminate genetic abnormalities To address these challenges, CRISPR/Cas9 gene editing
from the genome. Utilizing CRISPR/Cas9 for modifying techniques have been proposed as a means to achieve
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embryos, germline cells, and pluripotent stem cells in precise and targeted genome modifications, potentially
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human reproduction exhibits significant promise. advancing various aspects of reproduction. For
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However, the use of CRISPR gene editing to cure diseases instance, gene editing holds promise in treating fertility
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in embryos is a subject of controversy. While CRISPR/Cas9 issues such as tubal disease and low sperm counts.
is extensively employed in scientific research, utilizing In addition to these applications, the combined use of
germline genome editing in clinics raises ethical and CRISPR and ARTs has streamlined the editing of genomes
social concerns regarding the safety of future generations in embryos produced through techniques like IVF.
and the potential misuse of genome editing for human CRISPR/Cas proves particularly valuable in the context
enhancement. Despite these ethical considerations, of IVF. Embryos produced through IVF can undergo
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studies have demonstrated the preventive and curative CRISPR-mediated disruption or editing of specific genes,
potential of CRISPR-based gene editing technologies for presenting opportunities to prevent genetic illnesses or
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diseases caused by genetic mutations. Notably, CRISPR- enhance specific traits. Furthermore, CRISPR holds the
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Cas9 has been successfully used to delete faulty genes potential to enhance oocyte and sperm fertility within the
associated with Parkinson’s disease both in vitro and IVF setting. For instance, the CRISPR/dCas9 activation
in vivo. In a rat model of Parkinson’s disease, CRISPR- approach has demonstrated success in restoring oocyte
Cas9 effectively restored normal cellular functions and fertility by augmenting the levels of the sperm-oocyte
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alleviated Parkinson’s motor symptoms, suggesting its binding protein Juno. Overall, CRISPR technology has
potential application in treating diseases caused by specific the potential to enhance IVF outcomes and foster the
mutations, such as the A53T-SNCA mutation linked to exploration of novel applications for both female and male
Parkinson’s disease. 64 reproductive systems. 77
In addition, CRISPR gene editing aids in identifying The integration of CRISPR technology with ICSI has
damaging mutations in genetic diseases. For example, been instrumental in several investigations focusing on
CRISPR/Cas9 was employed to create Lynch syndrome- male fertility and spermatogenesis. CRISPR/Cas9, for
related missense variants in the MSH2 gene, a disorder instance, was utilized to create Tbc1d21 knockout mice,
induced by germline DNA mismatch repair gene which exhibited male sterility due to bent spermatozoa
mutations. The impact of these variants on cellular function flagella. While IVF proved ineffective for these mice, ICSI
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was examined, showcasing the potential of CRISPR in resulted in the birth of healthy offspring. In another study,
understanding and addressing genetic disorders. While CRISPR/Cas9 was employed to generate Iqcn-knockout
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concerns and moral ramifications surround the use of mice, which exhibited abnormal acrosome structures
CRISPR gene editing on human embryos, ongoing studies leading to male sterility. The failure of fertilization
explore the potential and limitations of CRISPR gene associated with Iqcn disruption was successfully managed
editing in embryos for various applications, including using ICSI and aided oocyte activation. These findings
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the development of large-animal research models and underscore the potential of CRISPR technology combined
the treatment of genetic and reproductive problems. 66-68 with ICSI to explore the genetic basis of male infertility
Further, research is needed to address ethical, safety, and develop viable treatments. 80

Volume 3 Issue 1 (2024) 6 https://doi.org/10.36922/gpd.2701