Enter the realm of gene editing technology, where the incredible CRISPR/Cas9 has set the stage for a true scientific revolution. This game-changing tool grants scientists unprecedented power, allowing them to delve into the very fabric of genes, potentially unlocking the cure for a myriad of genetic diseases. However, amid this excitement, lies a critical hurdle: delivering CRISPR/Cas9 precisely to specific tissues for effective clinical application. In recent years, researchers have made significant strides in developing strategies for tissue-specific delivery, unlocking the full potential of CRISPR/Cas9 for therapeutic purposes.
The successful application of CRISPR/Cas9 hinges on its ability to navigate the complex journey to the intended target cells without causing any unintended side effects. Scientists have explored numerous pathways to attain tissue-specific delivery, and amidst this gene-editing battleground, two prominent strategies emerge victorious: Passive-Targeting-Based Strategy and Ligand-Based Active Targeting Strategy.
Passive-Targeting-Based Strategy
Passive targeting relies on the interplay of physiological characteristics in the quest for selective delivery. This ingenious strategy exploits the diversity of vasculature, permeability, and retention, artfully distinguishing between normal and diseased tissues. Nanoparticles, carrying the CRISPR/Cas9 components, can be meticulously tailored with specific sizes, charges, and surface properties, facilitating their preferential accumulation in the target tissue. The enhanced permeability and retention effect (EPR) is a powerful guiding principle behind passive targeting. It enables nanoparticles to accumulate in tumor tissues due to their leaky blood vessels and impaired lymphatic drainage.
Ligand-Based Active Targeting Strategy
In contrast to passive targeting, active targeting involves nanoparticles equipped with specialized ligands that bind to overexpressed receptors on the target cell's surface. These ligands act like a magnet, drawing the nanoparticles to the precise tissue they need to reach. This method ensures the delivery of CRISPR/Cas9 to specific cell types while sparing healthy cells from any unintended effects.
In the fascinating world of active targeting, an array of ligands steps into the spotlight. These versatile molecules, from antibodies to peptides and beyond, reveal a remarkable penchant for binding with desired receptors. By employing ligand-based active targeting, researchers have made significant progress in delivering CRISPR/Cas9 to specific tissues such as the liver, lungs, and central nervous system.
Stimuli-Responsive Nanomaterials: Examples Related to CRISPR/Cas9 Delivery
Stimuli-responsive nanomaterials have emerged as another innovative approach for tissue-specific CRISPR/Cas9 delivery. These materials can respond to specific cues present in the target tissue microenvironment, triggering the release of the gene-editing machinery precisely where and when it is needed.
For instance, pH-responsive nanoparticles can take advantage of the acidic environment often found in tumor tissues. When these nanoparticles encounter a lower pH, they undergo changes in their structure, leading to the release of CRISPR/Cas9. Similarly, temperature-sensitive materials can be engineered to release their cargo in response to elevated temperatures associated with inflammation or infection.
Reference
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Sahel DK, Vora LK, Saraswat A, Sharma S, Monpara J, D'Souza AA, Mishra D, Tryphena KP, Kawakita S, Khan S, Azhar M, Khatri DK, Patel K, Singh Thakur RR. CRISPR/Cas9 Genome Editing for Tissue-Specific In Vivo Targeting: Nanomaterials and Translational Perspective. Adv Sci (Weinh). 2023, Comput Struct Biotechnol J. 2019, 17:1348-1359.
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