Unknown

Dataset Information

0

Selective elimination of long INterspersed element-1 expressing tumour cells by targeted expression of the HSV-TK suicide gene.


ABSTRACT: In gene therapy, effective and selective suicide gene expression is crucial. We exploited the endogenous Long INterspersed Element-1 (L1) machinery often reactivated in human cancers to integrate the Herpes Simplex Virus Thymidine Kinase (HSV-TK) suicide gene selectively into the genome of cancer cells. We developed a plasmid-based system directing HSV-TK expression only when reverse transcribed and integrated in the host genome via the endogenous L1 ORF1/2 proteins and an Alu element. Delivery of these new constructs into cells followed by Ganciclovir (GCV) treatment selectively induced mortality of L1 ORF1/2 protein expressing cancer cells, but had no effect on primary cells that do not express L1 ORF1/2. This novel strategy for selective targeting of tumour cells provides high tolerability as the HSV-TK gene cannot be expressed without reverse transcription and integration, and high selectivity as these processes take place only in cancer cells expressing high levels of functional L1 ORF1/2.

SUBMITTER: Chendeb M 

PROVIDER: S-EPMC5503529 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Selective elimination of long INterspersed element-1 expressing tumour cells by targeted expression of the HSV-TK suicide gene.

Chendeb Mariam M   Schneider Robert R   Davidson Irwin I   Fadloun Anas A  

Oncotarget 20170601 24


In gene therapy, effective and selective suicide gene expression is crucial. We exploited the endogenous Long INterspersed Element-1 (L1) machinery often reactivated in human cancers to integrate the Herpes Simplex Virus Thymidine Kinase (HSV-TK) suicide gene selectively into the genome of cancer cells. We developed a plasmid-based system directing HSV-TK expression only when reverse transcribed and integrated in the host genome via the endogenous L1 ORF1/2 proteins and an Alu element. Delivery  ...[more]

Similar Datasets

| S-EPMC9307584 | biostudies-literature
| S-EPMC3024463 | biostudies-literature
| S-EPMC5352197 | biostudies-literature
| S-EPMC5027595 | biostudies-literature
| S-EPMC6817450 | biostudies-literature
| S-EPMC5796146 | biostudies-literature
| S-EPMC3080381 | biostudies-literature
| S-EPMC4440683 | biostudies-literature
| S-EPMC8559978 | biostudies-literature
| S-EPMC8849481 | biostudies-literature