Life Sciences & Biotechnology
Title : | "New therapeutic approach for corneal dystrophy via CRISPR mediated SLC4A11 gene correction in an in-vitro and in-vivo system using advanced cRGD decorated lipo-polymeric nanoplexes" |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Muralidhar Ramappa, L.V. Prasad Eye Institute, Hyderabad, Telangana |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | muralidhar@lvpei.org |
Details
Executive Summary : | Corneal dystrophies are inherited disorders causing profound visual loss due to corneal opacities. Congenital hereditary endothelial dystrophy (CHED) and certain forms of Fuch's corneal endothelial dystrophy (FECD) are the major causes of pediatric corneal blindness in the developing world. Over 85 SLC4A11 mutations have been identified in CHED pathogenesis. Current treatments include corneal replacement, but these face challenges such as scarcity of donor corneas, allograft rejection, graft failure, post-surgical complications, and recurrence of primary pathology. CRISPR-Cas, a genome-editing tool, offers a suitable therapeutic approach for treating corneal dystrophies due to its targeted genome editing, potential for topical administration, and non-repetitive administration. However, viral-based CRISPR delivery can limit clinical translation due to safety concerns. To address this, a team has designed an array of cationic amphiphilic lipo-polymers with functional ligands that can efficiently package CRISPR-ribonucleoprotein to form nanoplexes and control their extra and intracellular trafficking. This proposal aims to apply these advanced nanoplexes to deliver CRISPR molecules targeting SLC4A11 mutations correction or mutated exonic replacement in in-vitro and in vivo studies. Primary endothelial cell culture derived from patient-specific surgical tissue will be used for the in-vitro study, while a customized SLC4A11 knock-in mice model carrying CHED-specific mutations will be developed for the in-vivo study. A preclinical study will assess safety, specificity, off-target, and recovery in the disease phenotype. This CRISPR-based gene editing approach will provide proof of concept for the efficacy of CRISPR-based effective, non-surgical therapeutic intervention, potentially applicable to many similar corneal ailments. |
Co-PI: | Dr. Deepak Chitkara, Birla Institute Of Technology And Science (BITS) Pilani, Jhunjhunu, Rajasthan-333031, Dr. Anshuman Verma, L.V. Prasad Eye Institute, Hyderabad, Telangana-500034 |
Total Budget (INR): | 66,22,340 |
Organizations involved