Role of Biomaterials in Enhancing CRISPR Delivery Efficiency and Safety

ABSTRACT The CRISPR‐Cas system has transformed genome editing, enabling unprecedented precision in the modification of genetic material. The lack of a clinically validated delivery mechanism to safely distribute CRISPR‐Cas components into targeted cells or tissues without causing toxicity or immune reactions is a major challenge to the therapeutic application of CRISPR‐based gene editing. Biomaterials have addressed this difficulty by providing a transformational solution that enhances delivery and fosters biocompatibility and safety of CRISPR systems. This article examines the various methods by which biomaterials can mitigate significant challenges associated with CRISPR delivery, including immune activation, adverse consequences, and insufficient cellular absorption. Lipid nanoparticles, polymeric carriers, and bioengineered hydrogels have demonstrated significant potential in safeguarding CRISPR components such as ribonucleoproteins (RNPs), plasmids, and mRNAs against enzymatic degradation. Nevertheless, these technologies do not provide a means to restrict these components to a particular cell inside an organism. These technologies can accomplish tailored delivery to particular tissues while reducing systemic toxicity. Moreover, genome editing attains greater precision when biomaterials respond to stimuli and modulate their release under physiological circumstances, including pH, temperature, and enzymatic activity of the surrounding environment. Recently, CRISPR therapeutics have enhanced safety by the utilization of biomaterial designs, including biodegradable and non‐immunogenic carriers. The combination of biomaterials with CRISPR technology establishes a novel generation of safer, more effective, and clinically applicable gene editing platforms. This manuscript examines biomaterials‐based CRISPR delivery methods, highlights existing limitations, and outlines future possibilities. Biomaterials are essential in realizing the complete therapeutic potential of CRISPR by overcoming these obstacles.