Lentiviruses (more commonly used) vs. gammaretroviruses (old technology)
Similarities
Both retroviruses
Insert DNA randomly into host genome using viral integrase enzyme, creating permanent genetic changes (cell passes modifications down to daughter cells)
Differences
Lentivirus (derived from HIV) - used for frequently today (2024)
can infect both dividing and non-dividing cells
DNA is actively transported into host’s nucleus
has a more complex viral genome
Gammaretrovirus - older technology, was only used first bc it was better understood vs. lentivirus (HIV) in the early days and had a simpler genome
only infects dividing cells
needs nuclear membrane to breakdown
simpler viral genome
Applications
Lentiviral vectors are good when you need:
Permanent gene integration
Stable, long-term expression
High efficiency delivery
Main drawback: random integration
cannot control where CAR genes integrate (pseudo-random integration)
risk of insertional mutagenesis (randomly-inserted genes can accidentally activate oncogenes, disrupt tumor suppressor genes)
variable CAR expression levels: if viral vector inserts gene in
highly transcriptionally active, open chromatin regions ⇒ high CAR expression
not very transcriptionally active chromatin region ⇒ low CAR expression
Real-world example of lentiviral vectors in action:
