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Gene & Protein in Disease Enhancing fertility with CRISPR

number of individuals over a relatively short period. A of embryos using CRISPR technology, resulting in the
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specific illustration of such consequences is observed altered CCR5 gene in a pair of newly born baby girls – a
in males experiencing infertility due to a mutation in gene crucial for recognizing human immunodeficiency
the AKAP3 gene, as depicted in Figure 2. This mutation virus (HIV) and rendering individuals susceptible to the
disrupts the proper functioning of AKAP3, a protein condition. The claimed purpose of editing the gene was
crucial for anchoring protein kinase A in processes like to protect the babies from HIV transmission, as the father
capacitation and hyperactivated motility. In addressing was HIV positive. However, subsequent studies revealed
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this challenge, CRISPR technology emerges as a promising potential adverse effects of CCR5 mutations, including
solution. By leveraging CRISPR, it becomes feasible to increased susceptibility to lethal infectious diseases
correct the genetic mutation in the AKAP3 gene, offering like influenza and a heightened risk of severe sclerosis,
a potential avenue for the treatment of male infertility potentially leading to premature death. 55,57
resulting from such genetic mutations. This utilization In a 2015 study, scientists utilized human tripronuclear
of CRISPR underscores the transformative potential of zygotes (3PN) at an early stage for CRISPR-based gene
CRISPR in mitigating hereditary reproductive disorders editing, specifically targeting the human endogenous
and advancing therapeutic interventions. β-globin gene. While the efficiency of CRISPR in cleaving
One of the most impactful instances of human germline and modifying the targeted gene was demonstrated,
genome editing was claimed by Chinese scientist Jiankui challenges such as mosaicism in the embryo and off-target
He. He asserted that he successfully modified the genomes mutations were identified. Overcoming these challenges is

A

A

B

Figure 2. Genetic mutation in the gene AKAP3 leads to infertility in the males. (A) Genetic mutation in the AKAP3 gene disrupts its function in anchoring
protein kinase A (PKA) (for capitation and hyperactivated motility), leading to abnormal protein. This disruption impairs localized phosphorylation
of flagellar proteins, compromising coordinated flagellar beating and reducing sperm motility. cAMP and calcium are also crucial. cAMP activates
PKA, regulating flagellar proteins’ phosphorylation. Calcium ions guide microtubule sliding, shaping the flagellar movement. Disruption due to AKAP3
mutation hampers these signals, reducing sperm motility. (B) CRISPR can be utilized to correct the genetic mutation, thereby serving as a potential agent
to cure male infertility arising due to genetic mutations.
Abbreviations: PGCs: Primordial germ cells; CRISPR: Clustered regularly interspaced short palindromic repeats.

Volume 3 Issue 1 (2024) 5 https://doi.org/10.36922/gpd.2701