Salvador Pérez-Mora1, Sandra Viridiana Salgado-Hernández1, Yunuén Daniela Solorio-Cendejas1, Alejandro Pérez-Gómez2, Consuelo Gómez-García1 and David Guillermo Pérez-Ishiwara1*
Received: January 08, 2024; Published: January 25, 2024
*Corresponding author: David Guillermo Pérez-Ishiwara, Molecular Biomedicine laboratory 1, ENMH, Instituto Politécnico Nacional. Guillermo Massieu Helguera 239, Col. La Escalera, C.P. 07320, Mexico City, Mexico
Alopecia, characterized by abnormal hair loss, is more than an aesthetic problem; it is a major psychosocial challenge affecting millions of people worldwide. Traditional treatments, such as finasteride and minoxidil, often offer limited solutions and come with side effects. As an alternative, CRISPR/Cas9, an advanced technique for targeted gene modification, is emerging as a powerful tool to tackle alopecia at its genetic roots. The use of CRISPR/Cas9 to stimulate hair growth has shown efficacy in several experimental models and holds promise for manipulating key genes at different phases of the hair cycle and influencing molecular pathways related to hair growth. Therefore, the objective of our research was to deepen and summarize the use of CRISPR/ Cas9 technology in editing genes involved in hair growth. This work provides a deeper understanding of the underlying genetic mechanisms and paves the way for personalized and effective therapy
Keywords: CRISPR/Cas9; Gene Editing; Alopecia; Hair Growth, Hair Cycle, Hair Follicle; Therapeutic Potential
The hair cycle comprises four stages: anagen (growth), catagen (regression), telogen (rest), and exogen (shedding) . Alopecia, characterized by abnormal hair loss, stems from an imbalance in these phases. This imbalance is triggered by factors such as genetic predispositions, stress, nutritional deficiencies, hormonal changes, infections, and lifestyle habits . According to the American Academy of Dermatology (AAD), androgenetic alopecia affects approximately 50% of men and 30% of women. In contrast, alopecia areata affects about 2% of the population of the world . Currently, the drugs finasteride and minoxidil, approved by the Food and Drug Administration (FDA), serve as primary treatments for alopecia. However, the use of these drugs can lead to adverse side effects . Despite advancements in pharmacological treatments and topical therapies, the efficacy of these solutions is often limited. In this context, the CRISPR/ Cas9 genetic editing technology (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9) emerges as a promising tool. It provides a novel approach to understanding and potentially treating alopecia at the molecular level . The CRISPR/ Cas9 offers high-precision genetic editing, which opens possibilities for innovative approaches in understanding and addressing alopecia. Its potential application in this field could revolutionize the management of hair growth by editing fundamental genes, thereby enabling the reversal or prevention of hair loss . This study discusses recent developments and perspectives on the use of CRISPR/Cas9 in hair research and the treatment of alopecia [7-15].
The CRISPR/Cas9 represents a novel and highly sophisticated technology, facilitating targeted gene editing through a precise molecular mechanism, as illustrated in Figure 1.
Currently, the efficacy of CRISPR/Cas9 in editing specific genes and assessing their impact on hair growth and hair cycle regulation is being extensively studied. This includes exploring how these genes modulate molecular pathways and understanding their significance. These assessments have been conducted across various murine models, as detailed in Table 1. Experimental advances with CRISPR/Cas9 open a promising horizon in the understanding and activation of the hair cycle at a molecular level. This technology represents an innovative alternative for hair regeneration and the treatment of alopecia, marking a significant advance in the field of dermatology and regenerative medicine.
Note: SRD5A2: Steroid 5 Alpha-Reductase 2, FGF5: Fibroblast Growth Factor 5, FGF21: Fibroblast Growth Factor 21, Tβ4: Thymosin Beta-4, VDR: Vitamin D Receptor, LAMA3: Laminin Subunit Alpha 3, PLCD1: Phospholipase C Delta 1, CCHCR1: Coiled-Coil α-Helical Rod Protein 1, VEGF: Vascular Endothelial Growth Factor, BMP2/4: Bone Morphogenetic Protein 2/4, Pi3k/Akt: Phosphoinositide 3-Kinase/Protein Kinase B, Mapk/Erk: Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase, VGF: VGF Nerve Growth Factor, Lef1: Lymphoid Enhancer-Binding Factor 1, and, Foxn1: Forkhead Box N1.
The role of CRISPR/Cas9 in editing critical genes to induce hair growth presents enormous opportunities, spanning from enhancing our understanding of genetic causes to developing personalized therapies. This technology holds the potential to prevent hair loss in individuals with a high genetic risk and aid in hair regeneration in advanced cases. However, there are challenges in clinical implementation, such as the need for precise genetic editing, effective delivery systems, and the minimization of adverse immune responses. Additionally, ethical, and regulatory considerations, public acceptance, and accessibility to these therapies must be considered. It is essential to conduct further research on the long-term effects of CRISPR/Cas9 and undertake clinical trials to ensure its safe application in humans.
CRISPR/Cas9 has revolutionized the approach to tackling alopecia, providing a deeper molecular understanding and the ability to induce hair growth through the editing or insertion of specific genes. These remarkable advances underscore the transformative potential of this molecular tool in hair gene therapy.
To CONAHCYT for their invaluable contribution through the postgraduate scholarship granted to S. P-M, and to the Instituto Politécnico Nacional.
The authors declared that there is no conflict of interest.