Target intelligence / Profile preview

Porcine endogenous retrovirus (PERV) (PERV)

Target
PERV
Molecular classification
Retrovirus, Endogenous retroviral element, Viral genome
01

Overview

Porcine endogenous retroviruses (PERVs) are proviral sequences integrated into the genome of all pigs, posing a significant hurdle for xenotransplantation. These sequences can produce infectious viral particles capable of infecting human cells, raising concerns about potential zoonotic outbreaks in transplant recipients (Niu et al., 2017; Denner, 2021). In the EGEN-2784 genome, a specific genetically modified porcine line developed by eGenesis, all functional copies of PERV have been inactivated using CRISPR-Cas9 technology (Kim et al., 2023). This is achieved by targeting the highly conserved polymerase (pol) gene across dozens of genomic locations simultaneously to prevent viral replication (Niu et al., 2017). The elimination of PERVs is a critical safety requirement for the clinical application of pig-to-human organ transplantation, such as the use of EGEN-2784 derived kidneys (eGenesis, 2023). While not a traditional pharmacological target, PERVs are the primary genomic targets for modification to ensure the long-term safety of xenografts (Denner, 2021). Monitoring for PERV activity remains a standard part of safety protocols in xenotransplantation trials (Kim et al., 2023).

Other names
PERV sequencesPorcine endogenous retroviral elementsPERV-APERV-BPERV-C
02

Mechanism of action

CRISPR-Cas9 mediated multiplexed genome editing to inactivate the viral polymerase (pol) gene, thereby preventing the assembly of infectious viral particles and eliminating the risk of zoonotic transmission.

03

Biological functions

Viral replicationGenomic integrationReverse transcription
04

Disease associations

ZoonosisInfectionXenotransplantation-associated viral transmission
05

Safety considerations

Zoonotic transmission to human recipientsRecombination with human endogenous retroviruses (HERVs)Off-target effects of multiplexed CRISPR-Cas9 editingPotential for insertional mutagenesis
06

Interacting drugs

CRISPR-Cas9

3 more in the full profile.

07

Biomarkers

PERV DNA copy numberPERV RNA expressionReverse transcriptase activity

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