Introduction to Retrovirus Vectors

Retrovirus vectors are developed from RNA viruses that belong to a viral family Retroviridae. Within the host cell these viruses can synthesize double-stranded DNA (dsDNA) from their RNA genomes using an enzyme known as reverse transcriptase. This DNA can then be integrated into the chromosome of the host cell using another enzyme carried by the virus, known as integrase. Stable integration of the DNA synthesized from the viral genome modifies the host cell, which now synthesizes viral proteins along with host proteins. When the modified host cell divides, the daughter cells retain copies of the viral genes.

The retrovirus genome usually comprises of three open reading frames:

  • Gap - Group-specific antigen: Encodes structural proteins that form the viral capsid.
  • Pol - Polymerase: Encodes the reverse transcriptase, protease, and integrase enzymes.
  • Env - Envelope: Encodes the viral envelope (surface and transmembrane glycoprotein) proteins.

 

Retrovirus Advantages

Retroviruses are the most common gene delivery vectors and are used in over 60-70% of human gene therapy clinical trials. This is attributed to the following reasons:

  • Retroviruses have high efficiency of gene transfer. These vectors allow for stable integration of the transgene into the host genome, facilitating long term expression.
  • Retroviruses can be pseudotyped with env proteins to infect a specific cell type or a broad range of target cells, as required.
  • Retroviruses have a higher packaging capacity (8 kb) compared to adenoviral and AAV vectors.