Internal Reference: 2025-065

Market Need聽

Although the field of gene-targeted therapies has been revolutionized over the past decade with the introduction of CRISPR technology (e.g., Casgevy clinically approved for treatment of sickle cell disease and transfusion-dependent 尾-thalassemia), Despite this success, modifications to the guide RNA (crRNA), or gRNA, are crucial for improving CRISPR-based gene therapies by enhancing specificity, reducing off-target effects, and increasing editing efficiency. However, complex nucleic acid-protein binding interactions within the CRISPR-Cas system make it difficult to fully modify the crRNA without negative impacting gene editing.

Technology Overview

The Cas12a system has the ability to lead the field of CRISPR therapeutics, with a shorter crRNA (~40 nucleotides), simplifying its synthesis. Additionally, it has an enhanced specificity compared to the Cas9 system. 黑料网爆吃瓜 has fully chemically modified the Cas12a crRNA by systematically replacing each position within the crRNA with nucleotide analogues while maintaining critical contacts with the protein. This work towards an RNA-free crRNA enables in vivogene editing without a carrier vehicle due to its resistance to nuclease degradation.

Commercial Advantages

• Readily synthesized with higher target specificity (i.e. less off-target effects) and the ability to target promotor regions
• Enhanced stability and bioavailability
• Enhanced potency of carrier-free delivery of CRISPR therapeutics

Additional Information

• Researcher: Masad Damha
• 笔补迟别苍迟蝉:听US Provisional (Filed)
• Keywords:聽Gene Therapy, Chemical Modifications