Messenger　RNA　(mRNA)　is　a　biomolecule　with　a　wide　range　of　promising　clinical　applications.　However,　the　unstable　nature　of　mRNA　and　its　susceptibility　to　degradation　by　ribonucleases　(RNases)　necessitate　the　use　of　specialized　formulations　for　delivery.　Polycations　are　an　emerging　class　of　synthetic　carriers　capable　of　packaging　nucleic　acids,　and　may　serve　as　suitable　RNase-resistant　formulations　for　mRNA　administration.　Here,　we　explore　the　application　of　VIPER　and　sunflower　polycations,　two　polycations　previously　synthesized　by　our　group,　for　the　delivery　of　mRNA　in　comparison　to　branched　poly(ethylenimine);　all　three　polycations　have　been　shown　to　efficiently　deliver　plasmid　DNA　(pDNA)　to　cultured　cells.　Despite　successful　mRNA　condensation　and　packaging,　transfection　studies　reveal　that　these　three　polycations　can　only　efficiently　deliver　mRNA　under　serum-free　conditions,　while　pDNA　delivery　is　achieved　even　in　the　presence　of　serum.　RNase　resistance　studies　confirm　that　nuclease　degradation　of　mRNA　cargo　remains　a　significant　barrier　to　mRNA　delivery　using　these　polycations.　These　results　emphasize　the　need　for　additional　strategies　for　nuclease　protection　of　mRNA　cargo　beyond　electrostatic　complexation　with　polycation.