The Kunjin Replicon

Replikun Biotech is commercializing a novel recombinant viral vector system suitable for immunotherapy, vaccine development and recombinant protein production.  The vector is derived from the Kunjin virus, a benign flavivirus endemic to Northern Australia.

Kunjin replicon vectors are based on the Kunjin virus RNA genome. Genes for Kunjin structural proteins have been essentially removed from the vector, and may be replaced by a therapeutic gene of interest. The Kunjin replicon also encodes seven non-structural Kunjin proteins (NS1- NS5) that guide the production of therapeutic protein and self-replication of the replicon in vivo.

Although the Kunjin replicon retains the ability to self-replicate inside cells, the absence of structural genes means that Kunjin replicon transfected cells are unable to produce infectious viral particles or escape and infect other cells.

The Kunjin Replicon

Replacement of the structural genes (C, prM and E) in the full length Kunjin genome (A) by a gene encoding for a heterologous protein of interest produces the Kunjin replicon (B).

Kunjin replicons can be delivered as plasmid DNA, as naked RNA, and as naked RNA packaged into virus like particles (VLPs).  Regardless of the delivery mode, once in the cytoplasm, Kunjin replicon RNA initiates self-replication leading to production of large amounts of replicon RNA resulting in the production of high levels of heterologous protein. 

VLPs currently provide the most efficient gene delivery system and outperform RNA and DNA in pre-clinical vaccine studies.  However, substantially less Kunjin DNA is needed compared with conventional DNA to produce similar immune responses upon immunisation. 

VLPs as delivery agents for Kunjin replicon system vectors.

A: VLPs injected into patients either subcutaneously or intramuscularly attach themselves to cells and initiate uptake.
B: VLPs are released into the cytoplasm of the cell.
C: VLPs are degraded in the cytoplasm, releasing its Kunjin replicon system vector payload, which self-replicates to produce multiple copies of itself.
D: The amplified Kunjin replicon vectors direct the cell’s protein synthesis machinery to produce therapeutic protein. New viral particles are never produced because the Kunjin replicon vectors lack the Kunjin structural protein genes.
E: Therapeutic proteins are produced in the cell, and processed according to function – antigens are processed to the cell surface for immune recognition; therapeutic proteins are secreted from the cell.

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