Target intelligence / Profile preview

BK polyomavirus messenger RNA (BKV mRNA)

Target
BKV mRNA
Molecular classification
Viral messenger RNA, Other
01

Overview

BK polyomavirus (BKV) messenger RNA (mRNA) is a vital component of the viral life cycle, serving as the template for the translation of proteins necessary for replication and structural assembly [7, 10]. BKV is a ubiquitous double-stranded DNA virus that remains latent in the renal tubular epithelial cells of healthy individuals but can reactivate under conditions of immunosuppression, such as following a kidney transplant [11, 18]. Reactivation leads to high levels of viral mRNA expression, which drives the production of the Large T-antigen for genome replication and capsid proteins like VP1 for virion formation [1, 12]. This process can result in BK virus-associated nephropathy (BKVAN), a leading cause of graft failure in transplant recipients [3, 10]. Therapeutic strategies targeting BKV mRNA include antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), which aim to silence viral gene expression with high specificity [2, 9]. For example, AIC-468 is an investigational ASO that inhibits the splicing of Large T-antigen pre-mRNA to suppress viral replication [2, 17]. Furthermore, the detection of specific BKV mRNA transcripts in urine serves as a non-invasive biomarker for diagnosing active infection and monitoring therapeutic efficacy [4, 16]. These RNA-targeted approaches offer a potential alternative to traditional antivirals, which often have limited efficacy or significant toxicity in the transplant setting [13, 18].

Other names
BK virus mRNABKPyV mRNABKV transcriptsBKV VP1 mRNABKV Large T-antigen mRNA
02

Mechanism of action

Antisense inhibition of mRNA splicing [2, 17] and RNA interference-mediated mRNA degradation [9, 14]

03

Biological functions

Viral protein synthesisViral replicationViral assemblyOther
04

Disease associations

InfectionOther
05

Safety considerations

Off-target effects [14]Renal accumulation and potential nephrotoxicity [2]Innate immune activation via Toll-like receptors [14, 15]Viral mutational escape [9]
06

Interacting drugs

AIC-468

1 more in the full profile.

07

Biomarkers

Urinary BKV VP1 mRNA [4, 16]Urinary BKV microRNA (bkv-miR-B1-5p) [1, 5, 6]BKV DNA load [3, 16]

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