Profile
I have been working on lipid nanoparticle mediated nucleic acid delivery for past 19 years. I completed my Ph.D. from IICT Hyderabad, in liposomal gene therapy, post-doc in Florida A&M University and inStem-Bengaluru. From 2015, I have been working as a sceintist at CSCR-Vellore. Our research is an interdisciplinary with an interface of chemistry and biology, emphasizes on lipid-mediated nucleic acid therapeutics. Primary goal is to translate the concept of nucleic acid therapy to a clinically viable application. To this end, we have been developing cationic lipids to deliver nucleic acids including pDNA, mRNA. Our disease models include nucleic acid therapeutics for hemophilia and mRNA-based vaccine for SARS-CoV2.
Current Focus Areas
mRNA vaccine for SARS-CoV2: We designed, synthesized developed mannose receptor targeting shikimoylated lipid nanoparticle system. Optimized 5’&3’ mRNA UTRs for superior translation towards developing a cross-reactive mRNA vaccine for multiple SARS-CoV2 strains.
mRNA therapeutics for Hemophilia: We developed a m1Ψ modified human FVIII mRNA with our liver-targeting lipid nanoparticle (Gal-LNP) system and evaluated its delivery efficiencies in vitro and Hemophilia A mouse models. m1Ψ-FVIII mRNA showed high therapeutic efficacy even up to 15 days in vivo in Hemophilia A mouse model.
Bio-inspired cationic lipid nanoparticles for delivering gene editing tools: We developed a novel lipid nanoparticle system that could efficiently deliver CRISPR tools, where Cas9 in pDNA, mRNA and protein forms than their respective commercial transfection reagents. Currently, we are exploring their applications in editing hematopoietic stem cells for treating beta-globinopathies.
Selected Publications
Mahalingam G, Rachamalla HK, Arjunan P, Karuppusamy KV, Periyasami Y, Mohan A, Subramaniyam K, M S, Rajendran V, Moorthy M, Varghese GM, Mohankumar KM, Thangavel S, Srivastava A, Marepally S*. SMART-lipid nanoparticles enabled mRNA vaccine elicits cross-reactive humoral responses against the omicron sub-variants. Molecular Therapy 2024, S1525-0016(24)00097-2. doi: 10.1016/j.ymthe.2024.02.028. PMID: 38414245
Brijesh Lohchania, Abisha Crystal Christopher, Porkizhi Arjunan, Gokulnath Mahalingam, Durga Kathirvelu, Aishwarya Prasannan, Vigneshwaran Venkatesan, Pankaj Taneja, Mohan Kumar KM, Saravanabhavan Thangavel* and Marepally S.* Diosgenin enhances liposome-enabled nucleic acid delivery and CRISPR/Cas9-mediated gene editing by modulating endocytic pathways, Front. Bioeng. Biotechnol., Sec. Preclinical Cell & Gene Therapy, 2023, doi.org/10.3389/fbioe.2022.1031049
Mahalingam G, Periyasami Y, Arjunan P, Subaschandrabose RK, Mathivanan TV, Mathew RS, Ramya Devi K, Premkumar PS, Muliyil J, Srivastava A, Moorthy M*, Marepally S*. Omicron infection increases IgG binding to spike protein of predecessor variants. J Med Virol. 2023 Dec 22. doi: 10.1002/jmv.28419.
Hari Krishnareddy Rachamalla, Chandrashekhar Voshavar, Porkizhi arjunan, Gokulnath Mahalingam, Rashmi Praksash Chowath, Rajkumar Banerjee*, Praveen Kumar Vemula*, Marepally S.* Skin permeable nano-lithocholic-lipidoid efficiently alleviates psoriasis-like chronic skin inflammations, ACS Applied Materials and Interfaces, 2022, 14(13):14859-14870
Vignesh R, Nivedhitha D, Nithin SR, Lokesh P, Joshua P, Chandrasekar G, Keerthiga A, Gokulnath M, Yogapriya M, Stacia W, Kirti P, Anila G, Dhiyaneshwaran S, Sandhiya G, Aswin AP, Ryo K, Yukio N, Poonkuzhali B, Rajasekaran R, Saravanabhavan T, Shaji R V, Merlin C, Srujan M, Alok S, KM Mohankumar* Targeted disruption of BCL11A-XL specific zinc finger motif for de-repression of fetal globin expression. Molecular Therapy, 2024 32(3):663-677.