Target intelligence / Profile preview

BK polyomavirus early pre-mRNA splice donor site (BKV early splice donor site)

Target
BKV early splice donor site
Molecular classification
Nucleic acid, RNA regulatory element
01

Overview

The BK polyomavirus (BKV) early pre-mRNA splice donor site is a pivotal genetic element located in the early region of the BKV genome, which encodes the Large T-antigen (LTAg) and small t-antigen (Sethi et al., 2012, Journal of Virology). This site facilitates the precise splicing required to generate the LTAg mRNA transcript, a protein that is mandatory for viral DNA replication and the subversion of host cell cycle control (Rinaldo et al., 2010, American Journal of Transplantation). In clinical settings, BKV reactivation is a major cause of BKV-associated nephropathy (BKVAN) and hemorrhagic cystitis in immunocompromised patients, such as organ transplant recipients. Therapeutic strategies targeting this splice donor site primarily utilize antisense oligonucleotides (ASOs) designed to bind the pre-mRNA sequence via Watson-Crick base pairing. This binding sterically blocks the spliceosome from accessing the donor site, thereby preventing the formation of mature LTAg mRNA and effectively halting the viral replication cycle (Giraud et al., 2010, Antiviral Research). This approach is particularly relevant for treating BKV-associated nephropathy in kidney transplant recipients, where uncontrolled viral reactivation can lead to graft loss.

Other names
BK virus LTAg splice donor siteBKV early region 5' splice siteBKPyV early pre-mRNA splice siteBKV T-antigen splice donor
02

Mechanism of action

Steric blocking of the splice donor site to inhibit the production of Large T-antigen mRNA, thereby preventing viral DNA replication.

03

Biological functions

Viral replicationRNA splicingViral gene expression
04

Disease associations

BK virus-associated nephropathyHemorrhagic cystitisPolyomavirus infection
05

Safety considerations

Off-target hybridization to host RNARenal toxicityDelivery efficiency to infected tubular epithelial cells
06

Interacting drugs

Antisense oligonucleotides (experimental)

1 more in the full profile.

07

Biomarkers

BKV DNA load in plasmaBKV DNA load in urineLarge T-antigen expression

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