*6.2. Combination of VSV with Polycations*

As mentioned above, some PDAC cell lines, including HPAF-II, are highly resistant to VSV due to a combination of a constitutive antiviral state and type I IFN-independent impaired VSV attachment. It was determined that the source of the impairment to attachment was not a result of mutations to the LDLR or its lowered expression levels, but rather by some other mechanism [60]. We have shown that treatment of cells with polycations improved LDLR-independent virus attachment, as both the cellular membrane and the viral envelope have negative net charges, and the polycations serve to counteract the repulsive electrostatic effects of the lipid barriers. Earlier studies showed a similar effect on cells treated with either DEAE-Dextran or polybrene before infection [191,192]. A novel combinatorial treatment with ruxolitinib and polycations demonstrated improved overall VSV replication and oncolysis and accelerated VSV replication kinetics compared to treatment with ruxolitinib only [60].
