KFU. Card publication. Functionality of a bicistronic construction containing HEXA and HEXB genes encoding β-hexosaminidase A for cell-mediated therapy of GM2 gangliosidoses

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FUNCTIONALITY OF A BICISTRONIC CONSTRUCTION CONTAINING HEXA AND HEXB GENES ENCODING β-HEXOSAMINIDASE A FOR CELL-MEDIATED THERAPY OF GM2 GANGLIOSIDOSES

Form of presentation

Articles in international journals and collections

Year of publication

2022

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Authors, employees of KFU

Aymaletdinov Aleksandr Maazovich, author

Rizvanov Albert Anatolevich, author

Soloveva Valeriya Vladimirovna, author

Chulpanova Darya Sergeevna, author

Authors, postgraduates KFU

Shaymardanova Alisa Almazovna, postgraduate kfu

Bibliographic description in the original language

Tay-Sachs disease and Sandhoff disease are severe hereditary neurodegenerative disorders caused by a deficiency of β-hexosaminidase A (HexA) enzyme, which results in the accumulation of GM2 gangliosides in the nervous system cells. In this work, we analyzed the efficacy and safety of cell-mediated gene therapy for Sandhoff disease and Sandhoff disease using a bicistronic lentiviral vector encoding cDNA of HexA α- and β-subunit genes separated by the nucleotide sequence of a P2A peptide (HEXA-HEXB). The functionality of the bicistronic construct containing the HEXA-HEXB genetic cassette was analyzed in a culture of HEK293T cells and human umbilical cord blood mononuclear cells (hUCBMCs). Our results showed that the enzymatic activity of HexA in the conditioned medium harvested from genetically modified HEK293T-HEXA-HEXB and hUCBMCs-HEXA-HEXB was increased by 23 and 8 times, respectively, compared with the conditioned medium of native cells. Western blot analysis showed that hUCBMCs-HEXA

Keywords

bicistronic vector; cell-mediated gene therapy; GM2 gangliosidosis; P2A peptide; Sandhoff disease; Tay-Sachs disease; umbilical cord blood mononuclear cells; β-hexosaminidase

The name of the journal

Neural Regeneration Research

Please use this ID to quote from or refer to the card

https://repository.kpfu.ru/eng/?p_id=268794&p_lang=2

Resource files

File name	Size (MB)	Format
NRR_17_122.pdf	1,51	pdf	show / download

Full metadata record

Field DC	Value	Language
dc.contributor.author	Aymaletdinov Aleksandr Maazovich	ru_RU
dc.contributor.author	Rizvanov Albert Anatolevich	ru_RU
dc.contributor.author	Soloveva Valeriya Vladimirovna	ru_RU
dc.contributor.author	Chulpanova Darya Sergeevna	ru_RU
dc.contributor.author	Shaymardanova Alisa Almazovna	ru_RU
dc.date.accessioned	2022-01-01T00:00:00Z	ru_RU
dc.date.available	2022-01-01T00:00:00Z	ru_RU
dc.date.issued	2022	ru_RU
dc.identifier.citation	Tay-Sachs disease and Sandhoff disease are severe hereditary neurodegenerative disorders caused by a deficiency of β-hexosaminidase A (HexA) enzyme, which results in the accumulation of GM2 gangliosides in the nervous system cells. In this work, we analyzed the efficacy and safety of cell-mediated gene therapy for Sandhoff disease and Sandhoff disease using a bicistronic lentiviral vector encoding cDNA of HexA α- and β-subunit genes separated by the nucleotide sequence of a P2A peptide (HEXA-HEXB). The functionality of the bicistronic construct containing the HEXA-HEXB genetic cassette was analyzed in a culture of HEK293T cells and human umbilical cord blood mononuclear cells (hUCBMCs). Our results showed that the enzymatic activity of HexA in the conditioned medium harvested from genetically modified HEK293T-HEXA-HEXB and hUCBMCs-HEXA-HEXB was increased by 23 and 8 times, respectively, compared with the conditioned medium of native cells. Western blot analysis showed that hUCBMCs-HEXA	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/eng/?p_id=268794&p_lang=2	ru_RU
dc.description.abstract	Neural Regeneration Research	ru_RU
dc.language.iso	ru	ru_RU
dc.subject		ru_RU
dc.title	Functionality of a bicistronic construction containing HEXA and HEXB genes encoding β-hexosaminidase A for cell-mediated therapy of GM2 gangliosidoses	ru_RU
dc.type	Articles in international journals and collections	ru_RU