The instant disclosure describes a novel genotype and phenotype assay to elucidate and/or evaluate new potential HIV integrase inhibitors, but also currently approved and experimental compounds that target protease, reverse transcriptase, and RNaseH. This assay allows studying linked mutations and mutational patterns that occur under HAART and experimental therapies.

The instant disclosure describes a novel genotype and phenotype assay to elucidate and/or evaluate new potential HIV integrase inhibitors, but also currently approved and experimental compounds that target protease, reverse transcriptase, and RNaseH. This assay allows studying linked mutations and mutational patterns that occur under HAART and experimental therapies.

There are disclosed hybrid proteins comprising at least one signal sequence; at least one DNA binding domain; and at least one cell penetrating peptide (CPP) domain. In embodiments the CPP domain is a TAT domain, and the DNA binding domain is a HU domain. There is also disclosed the use of the hybrid proteins to introduce exogenous DNA into target cells, and methods for introducing exogenous DNA into target cells using the hybrid proteins.

Disclosed are compositions and methods related to replication deficient Sindbis viruses that are able to function as controls for nucleic acid diagnostic assays (e.g., nucleic acid sequencing based assays and/or nucleic acid amplification based assays).