Engineering nucleic acid constructs for lymphoma therapy

Serine is an essential metabolite in cancer cells. In addition to being imported from the extracellular environment, serine can be synthesized through de novo serine synthesis (DNSS), a pathway that branches off glycolysis. Interestingly, unlike normal cancer cells, Natural killer/T cell lymphoma (N...

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Main Author: Sreevidya
Other Authors: -
Format: Final Year Project (FYP)
Language:English
Published: Nanyang Technological University 2024
Subjects:
Online Access:https://hdl.handle.net/10356/176326
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author Sreevidya
author2 -
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Sreevidya
author_sort Sreevidya
collection NTU
description Serine is an essential metabolite in cancer cells. In addition to being imported from the extracellular environment, serine can be synthesized through de novo serine synthesis (DNSS), a pathway that branches off glycolysis. Interestingly, unlike normal cancer cells, Natural killer/T cell lymphoma (NKTL) does not express phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme of DNSS. However, NKTL patients who experience prolonged survival have higher tumoral PHGDH expression levels, suggesting PHGDH may offer an advantage to NKTL patients by affecting the growth of NKTL cells. Previous experiments in vitro introducing PHGDH into NKS1 did not affect their growth and viability. To aid ongoing laboratory efforts in understanding the role of PHGDH in NKTL in vivo, we developed a workflow for producing transfection-competent PHGDH mRNA-lipid complexes. The synthesis, lipid encapsulation, and transfection of PHGDH mRNA were achieved in NKYS. However, transfection was unsuccessful in NKS1 and activated primary T and NK cells. The transfection of PHGDH mRNA-lipid complexes into NKTL and primary T and NK cells will allow us to study their impact on cell functionality, including cytokine production. Our goal is to utilize these complexes for intratumoral injections in vivo to uncover the effects of PHGDH on tumor growth.
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spelling ntu-10356/1763262024-05-20T15:33:08Z Engineering nucleic acid constructs for lymphoma therapy Sreevidya - School of Biological Sciences A*STAR Singapore Immunology Network Wang Liang Wei Wang_Liang_Wei@immunol.a-star.edu.sg Medicine, Health and Life Sciences Science::Biological sciences Serine is an essential metabolite in cancer cells. In addition to being imported from the extracellular environment, serine can be synthesized through de novo serine synthesis (DNSS), a pathway that branches off glycolysis. Interestingly, unlike normal cancer cells, Natural killer/T cell lymphoma (NKTL) does not express phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme of DNSS. However, NKTL patients who experience prolonged survival have higher tumoral PHGDH expression levels, suggesting PHGDH may offer an advantage to NKTL patients by affecting the growth of NKTL cells. Previous experiments in vitro introducing PHGDH into NKS1 did not affect their growth and viability. To aid ongoing laboratory efforts in understanding the role of PHGDH in NKTL in vivo, we developed a workflow for producing transfection-competent PHGDH mRNA-lipid complexes. The synthesis, lipid encapsulation, and transfection of PHGDH mRNA were achieved in NKYS. However, transfection was unsuccessful in NKS1 and activated primary T and NK cells. The transfection of PHGDH mRNA-lipid complexes into NKTL and primary T and NK cells will allow us to study their impact on cell functionality, including cytokine production. Our goal is to utilize these complexes for intratumoral injections in vivo to uncover the effects of PHGDH on tumor growth. Bachelor's degree 2024-05-15T05:07:09Z 2024-05-15T05:07:09Z 2024 Final Year Project (FYP) Sreevidya (2024). Engineering nucleic acid constructs for lymphoma therapy. Final Year Project (FYP), Nanyang Technological University, Singapore. https://hdl.handle.net/10356/176326 https://hdl.handle.net/10356/176326 en application/pdf Nanyang Technological University
spellingShingle Medicine, Health and Life Sciences
Science::Biological sciences
Sreevidya
Engineering nucleic acid constructs for lymphoma therapy
title Engineering nucleic acid constructs for lymphoma therapy
title_full Engineering nucleic acid constructs for lymphoma therapy
title_fullStr Engineering nucleic acid constructs for lymphoma therapy
title_full_unstemmed Engineering nucleic acid constructs for lymphoma therapy
title_short Engineering nucleic acid constructs for lymphoma therapy
title_sort engineering nucleic acid constructs for lymphoma therapy
topic Medicine, Health and Life Sciences
Science::Biological sciences
url https://hdl.handle.net/10356/176326
work_keys_str_mv AT sreevidya engineeringnucleicacidconstructsforlymphomatherapy