- Bio- Manufacturing
- AMRIT Grants, Ind - CEPI
Genome Editing Technologies (GET) Applications in Healthcare
Over the past few years, advances in genome editing technologies are making constant headlines. Being precise, relatively inexpensive, easy-to-use, and remarkably powerful, genome editing technologies have the potential to transform biological research and can greatly impact human healthcare solutions. Genome engineering represents the next step of evolution in our ability to analyze and edit the genetic information of various organisms including humans. The advances in genome editing can be traced back to quiet beginnings in the 1990s.However, the current surge in the number and range of applications of genome editing technologies largely owes to the introduction of the CRISPR-Cas9 – a genome-editing tool that can be used to make precise and targeted changes in the DNA sequence with much ease. The simplicity of the CRISPR platform, compared with the earlier tools, has led to its rapid adoption and wide expansion of its applications in healthcare.
Recognizing the power of Genome Editing techniques to study and manipulate the genome, the DBT has been engaged in promoting research and innovation in the area of genome engineering technologies and their applications in healthcare to make them accessible and affordable for wider use. Efforts have been made to encourage R&D programs in emerging genome engineering technologies and their applications in healthcare throughfocused calls for proposals in different areas such as development of new methods, tools, processes and platforms for genome editing, improvement of existing genome-editing methods, and novel applications of genome editing technologies inhealthcare.
Aims and Objectives of the Programme
- To drive research to develop new tools and methods for genome editing for basic and translational researchfor healthcare applications
- To facilitate establishment ofaccessible platforms facilities on emerging genome editing technologies for healthcare applications
- Improvement of existing genome editing technology platforms toward better throughput, precision, and safety
- Application of Genome Editing Technologies to address specific unmet needs in the areas of Human Health
- Human Resource Development in state-of-the-art Genome Editing Technologies and their applications in healthcare
Priority Areas
- Development of new cutting-edge tools and technologies for high-throughput, preciseand efficient genome editing for healthcare applications
- Improvement of existing genome editing technology platforms such as CRISPR/Cas and TALENs for ease and precision in healthcare applications
- Development of efficient and high throughput genome editing platforms in a wide range of laboratory animal models for catering to basic biomedical research and human disease modelling
- Integrating stem cell technology and embryo manipulation technologies with genome editing to develop xenotransplantation models
- Development of genome editing-based therapeutic solutions for the most prevalent rare and genetic disorders in India
- Capacity building in cutting-edge Genome Editing Technologies through workshops and training programmes
Major Programs and Initiatives
- Individual-centric and multi-institutional R&D projects on Genome Editing Technologies and their Applications
The Department has supported more than80 individual-centric and multi-institutional R&D projects on Genome Editing Technologies Applications in Healthcare in the last five years. A few of the most important scientific advancesfrom some of the R&D projects supported are:
- Using CRISPR-Cas-based gene editing system, the Role of Plasminogen Activator Inhibitor Type-1 (PAI-1) in the pathogenesis of tissue fibrosis –the excessive scarring of tissue which compromises its function has been established. Despite contributing to one-third of all deaths worldwide, there is no effective treatment, to date, for fibrosis. This study has established PAI-1 as a novel drug target and pharmacologically targeting this protein may be an effective treatment for combating fibrosis.
- Using shRNA-mediated gene silencing, phosphatases and kinases playing significant role in lysosome function, Endoplasmic Reticulum stress, protein trafficking and cellular senescence have been identified. This has been instrumental in delineating a few novel regulators of cellular homeostasis and has led to the identification of multiple potential drug targets for lysosomal storage disorders.
- A method has been developed using CRISPR-Cas for the targeted tracking of oncogenes in living cells through live-cell imaging approaches. This method can be applied to understand the effect of how chemotherapeutic agents act on the expression, localization and dynamics of oncogenes, such as C-MYC, CCND1, K-RAS and ERBB2 in the nucleus.
- CRISPR-based technologies in combination with single-effector nucleases are being utilized for development of diagnostics for viral diseases, such as AIDS and Hepatitis, and experimental therapeutics for genetic and complex diseases.
- Bioliposome mediated system has been developed for highly efficient intracellular delivery of genome-editing tools for therapeutic applications
Quantitative Outcome (Last five years)
Output | Number |
Scientists supported | 228 |
Projects supported | 144 |
Manpower (JRF/SRF/RA etc.) supported | 307 |
Publications | 105 |
Patents filed/granted | 7 |
Technologies / Products developed | 6 |
Workshop/Training programmes organized | 5 |
KeyPublications(Last five years)
Lohani N, Bhargava N, Munshi A, Ramalingam S (2018) Pharmacological and molecular approaches for the treatment of β-hemoglobin disorders. J Cell Physiol. 233 (6): 4563-4577.
Singh A, Srivastava N, Amit S, Prasad S, Misra M, Ateeq B. (2018) Association of AGTR1 (A1166C) and ACE (I/D) polymorphisms with Breast Cancer risk in North Indian population. Translational Oncology. Vol 11(2), doi.org/10.1016/j.tranon.2017.12.007). p233–242.
Bhatia V, Yadav A, Tiwari R, Nigam S, Goel S, Carskadon S, Gupta N, Goel A, Palanisamy N, AteeqB . Epigenetic silencing of miRNA-338-5p and miRNA-421 drives SPINK1-positive prostate cancer. Clinical Cancer Research. 2019 May 1;25(9):2755-2768. doi: 10.1158/1078-0432.CCR-18-3230.
Exploring membrane permeability of tomatidine in lipid mediated nucleic acid transfections. Vignesh K. Rangasami, BrijeshLochania, ChandrashekharVoshavar,Harikrishna R. Rachamalla, RajkumarBanerjee,AshishDayani, SaravanabhavanThangavel,Praveen K. Vemula , and SrujanMarepally . BBA Biomembranes, 2019 1861(1):327-334.
Bhargava N, Jaitly S, Goswami S, Jain S, Chakarborty D, Ramalingam S (2019) Generation and characterization of induced pluripotent stem cell line (IGIBi001-A) from a sickle cell anemia patient with homozygous β-globin mutation. Stem Cell Res14;39:101484.
Acharya S, Mishra A, Paul D, Ansari AH, Azhar M, Kumar M, Rauthan R, Sharma N, AichM, Sinha D, Sharma S, Jain S, Ray A, Jain S, Ramalingam S, Maiti S, Chakraborty D. (2019) Francisellanovicida Cas9 interrogates genomic DNA with very high specificity and can be used for mammalian genome editing. Proc Natl AcadSci U S A. 15;116(42):20959-20968.
Jana D, Kale HT, Shekar PC (2019). Generation of Cdx2-mCherry knock-in murine ES cell line to model trophectoderm and intestinal lineage differentiation. Stem Cell Res.; 39:101521. doi: 10.1016/j.scr.2019.101521. PMID: 31400702.
Ramdas P, Sahu AK, Mishra T, Bhardwaj V, Chande A. (2020). From entry to egress: Strategic exploitation of the cellular processes by HIV-1. Frontiers in Microbiology,11; 3021
Hussain MD, Bhardwaj V, Giri A, Chande A, Patra A. (2020). Multifunctional Ionic Porous Frameworks Based on Triaminoguanidinium for CO2 Conversion and Combating Microbes. Chemical Science,11;7910.
Balaji, S., &Vanniarajan, A. (2020). Implication of Pseudo Reference Genes in Normalization of Data from Reverse Transcription-Quantitative PCR. Gene, 757, 144948. https://doi.org/10.1016/j.gene.2020.144948
Singh A, Srivastava N, Yadav A, Ateeq B . Targeting AGTR1/NF-κB /CXCR4 axis by miR-155 attenuates oncogenesis in Glioblastoma. Neoplasia. 2020 Sep 4;22(10):497-510. doi: 10.1016/j.neo.2020.08.002.
Lunge, A., Gupta, R., Choudhary, E., & Agarwal, N. (2020) The unfoldase ClpC1 of Mycobacterium tuberculosis regulates the expression of a distinct subset of proteins having intrinsically disordered termini. J. Biol. Chem; doi: 10.1074/jbc.RA120.013456
Chandradoss KR, Chawla B, Dhuppar S, Nayak R, Ramachandran R, Kurukuti S, Mazumder A and Sandhu KS (2020). CTCF mediated genome architecture regulates the dosage of mitotically stable mono-allelic expression of autosomal genes. Cell Reports 33, 108302.
Nilavar, N.M., Nishana, M., Paranjape, A.M., Mahadeva, R., Kumari, R., Choudhary, B., Raghavan, S.C. (2020). Znc2 module of RAG1 contributes towards structure-specific nuclease activity of RAGs. Biochem J ,477(18).
Goutham, S., Kumari, I., Pally, D., Singh, A., Ghosh, S., Akhter, Y. &Bhat, R. (2020) Mutually exclusive locales for N-linked glycans and disorder in human glycoproteins. Sci Rep, 10(1): 6040.
Raut, G. K., Manchineela, S., Chakrabarti, M., Bhukya, C. K., Naini, R., Venkateshwari, A., ... & Bhadra, M. P. (2020). Imine stilbene analog ameliorate isoproterenol-induced cardiac hypertrophy and hydrogen peroxide-induced apoptosis. Free Radical Biology and Medicine, 153, 80-88.
Dwivedy, A., Ashraf, A., Jha, B., Kumar, D., Agarwal, N., & Biswal, B.K. (2021) De novo histidine biosynthesis protects Mycobacterium tuberculosis from host IFN-γ mediated histidine starvation. CommunBiol 4, 410. https://doi.org/10.1038/s42003-021-01926-4.
Gani, Z., Boradia, V.M., Kumar, A., Patidar, A., Talukdar, S., Choudhary, E., Singh, R., Agarwal, N., Raje, M., &Raje, C. I., (2021) Mycobacterium tuberculosis Glyceraldehyde‐3‐phosphate dehydrogenase plays a dual role‐as an adhesin and as a receptor for Plasmin(ogen). Cell Microbiol. 23(5):e13311.
Pally, D. & Bhat, R. (2021) N-terminal tail prolines of Gal-3 mediate its oligomerization/phase separation. Proc Nat AcadSci USA, 118(25): e2107023118.
Thakur P, Bhargava N, Jaitly S, Gupta P, Saroja, Padma P, Jain S, Bhattacharya S, Ramalingam S (2021). Establishment and characterization of induced pluripotent stem cell line (IGIBi002-A) from a β-thalassemia patient with IVS1-5 mutation by non-integrating reprogramming approach. Stem Cell Res. doi.org/10.1016/j.scr.2020.102124.
Ramdas P, Bhardwaj V, Singh A, Vijay N, Chande A. (2021). Coelacanth SERINC2 inhibits HIV-1 infectivity and is counteracted by envelope glycoprotein from foamy virus. Journal of Virology, 95(13);e0022921.
Pant, C., Chakrabarti, M., Mendonza, J. J., Ganganna, B., Pabbaraja, S., & Pal Bhadra, M. (2021). Aza-Flavanone Diminishes Parkinsonism in the Drosophila melanogaster Parkin Mutant. ACS chemical neuroscience, 12(23), 4380-4392.
Nagar, D., James, T.K., Mishra, R., Guha, S., Burgess, S.M. and Ghose, A. (2021) The Formin Fmn2b Is Required for the Development of an Excitatory Interneuron Module in the Zebrafish Acoustic Startle Circuit. eNeuro, 8 (4) ENEURO.0329-20.2021; DOI: https://doi.org/10.1523/ENEURO.0329-20.2021
Bahl, V., Chaddha, K., Mian, S.Y. et al. (2021) Genetic disruption of Plasmodium falciparum Merozoite surface antigen 180 (PfMSA180) suggests an essential role during parasite egress from erythrocytes. Sci Rep 11, 19183. https://doi.org/10.1038/s41598-021-98707-0
Sharma, S., &Rikhy, R. (2021). Spatiotemporal recruitment of RhoGTPase protein GRAF inhibits actomyosin ring constriction in Drosophila cellularization. eLife 2021;10:e63535
Sharma, S. and Rikhy, R. (2021). Spatiotemporal recruitment of RhoGTPase protein GRAF inhibits actomyosin ring constriction in Drosophila cellularization. Elife 10: e63535.
Priya S, Kaur E, Kulshrestha S, Pandit A, Gross I, Kumar N, Agarwal H, Khan A, Shyam R, Bhagat P, Prabhu JS, Nagarajan P, Deo SVS, Bajaj A, Freund JN, Mukhopadhyay A, Sengupta S (2021). CDX2 inducible microRNAs sustain colon cancer by targeting multiple DNA damage response pathway factors. J Cell Sci. 134(15): jcs258601.
Kaur E, Agrawal R, Sengupta S (2021). Functions of BLM helicase in cells: is it acting like a double-edged sword?Front Genet. 12:634789.
Hussain M, Mohammed A, Saifi S, Khan A, Kaur E, Priya S, Agarwal H, Sengupta S (2021). MITOL-dependent ubiquitylation negatively regulates the entry of PolA into mitochondria. PLoS Biol.19(3):e3001139.
Soory A, Ratnaparkhi GS (2022). SUMOylation of Jun fine-tunes the Drosophila gut immune response. PLoSPathog. doi: 10.1371/journal.ppat.1010356.
Mishra T, Bhardwaj V, Ahuja N, Gadgil P, Ramdas P, Shukla S, and Chande A. (2022) Improved loss-of-function CRISPR/Cas9 genome editing in human cells concomitant with inhibition of TGFβ signaling. Molecular Therapy : Nucleic Acid (in press).
Hithavan R, Shireesha M, Porkizhi A, Vigneshwaran V, Saravanabhavan T, Srujan M, Srilakshmi P, (2022) Influence of Hydrophobicity in Hydrophilic Region of Cationic Lipids on Enhancing Nucleic Acid Delivery and Gene Editing, ACS Applied Bio Materialshttps://doi.org/10.1021/acsabm.1c01226
Nithin SR, Beeke W, Stacia KW, Keerthi P, Gokulnath M, Jonathan V, Aswin AP, Poonkuzhali B, Yukio N, Ryo K, Saravanabhavan T, Srujan M, Shaji R V, Alok S, Merlyn C. Mark AD, Jacob EC, Mohankumar KM, (2022) Identification of novel HPFH-like mutations by CRISPR base editing that elevate the expression of fetal hemoglobin ELife;11:e65421. doi: 10.7554/eLife.65421.
Christopher AC, Venkatesan V, Karuppusamy KV, Srinivasan S, Babu P, Azhagiri MKK, Chambayil K, Bagchi A, Rajendiran V, Ravi NS, Kumar S, Marepally SK, Mohankumar KM, Srivastava A, Velayudhan SR, Thangavel S. (2022) Preferential Expansion of Human CD34+CD133+CD90+ Hematopoietic Stem Cells Enhances Gene-Modified Cell Frequency for Gene Therapy. Hum Gene Ther.; 33(3-4):188-201. doi: 10.1089/hum.2021.089.
List of Patents Applied
- Nain Vikrant, Tomar Pradeep, Suman (2020). Synthetic gene coding for FokI nuclease domain in programmable nucleases for genome editing. (India, Patent Application. Number: 202011039103)
- Nain Vikrant, Tomar Pradeep, Suman (2020). Synthetic gene coding for TET1 catalytic domain in programmable enzymes for epigenome editing. (India, Patent Application. Number: 202011039104)
- Nain Vikrant, Tomar Pradeep, Suman (2020). Synthetic gene coding for p65 subunit of NF-Kappa B transcription activation domain in programmable transcription factors. (India, Patent Application. Number: 202011039105)
- Nain Vikrant, Tomar Pradeep, Suman (2020). Synthetic gene coding for VP64 transcription activation domain in programmable transcription factors. (India, Patent Application. Number: 202011039106)
- Nain Vikrant, Tomar Pradeep, Suman (2020). Synthetic gene coding for KRAB transcription repression domain in programmable transcription repressors. (India, Patent Application. Number: 202011039107)
- Sandeep M Eswarappa, Lekha E Manjunath (2021). CRISPR-dCAS13 system, composition, and method to induce translational readthrough across stop codons. (India/IPO: 202141058043)
- KurukutiSreenivasulu and Gautam Das (2021). Method of pooling multiple reverse indexed DNA/RNA samples and adding single indexed forward primer and application thereof: India (Patent Application No: 202041030440)
Contacts Concerned Officer for more Information
Programme Head | Dr. Alka Sharma, Scientist H |
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alka[at]dbt[dot]nic[dot]in | |
Phone No. | 011-24363699 |
Programme Officer | Phone No. | |
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Dr. Vaishali Panjabi, Scientist F | vaishalip[dot]dbt[at]nic[dot]in | 011-24366268 |
Dr. Kamakshi Chaithri P, Scientist D | kamakshi[dot]c[at]dbt[dot]nic[dot]in | 011-24360295 |