Various retroviruses with distinct advantages for gene delivery have been modified and used in clinical trials.
Advanced engineering of a mini-intronic plasmid (MIP) system designed
to carry a therapeutic gene can significantly enhance the expression of
the transgene delivered using an adeno-associated viral (AAV) vector.
‘Advanced engineering of a mini-intronic plasmid (MIP) system designed to carry a therapeutic gene can significantly enhance the expression of the transgene delivered using an adeno-associated viral (AAV) vector by up to 40 to 100-fold.’
The ability to increase transgene expression by up to 40 to 100-fold,
which would reduce the cost of manufacturing and perhaps also lessen the
immune response of AAV/MIP-based gene therapy, is reported in Human
Authors Jiamiao Lu, Feijie Zhang, and Mark Kay, Stanford University,
Palo Alto, CA, and James Williams and Jeremy Luke, Nature Technology
Corp., Lincoln, NE, describe the modified MIP expression system in the
article entitled "A 5' Non-coding Exon Containing Engineered Intron Enhances Transgene Expression from Recombinant AAV Vectors in vivo."
The researchers discuss the potential implications of enhanced
transgene expression on the doses needed to achieve a therapeutic
response and the flexibility the small intronic sequences offer,
allowing them to be used in both DNA plasmids and viral delivery
"Careful observation of the expression characteristics of different
vector designs sometimes leads to unexpected findings," says
Editor-in-Chief Terence R. Flotte, Celia and Isaac Haidak Professor
of Medical Education and Dean, Provost, and Executive Deputy Chancellor,
University of Massachusetts Medical School, Worcester, MA.
case, the authors found that a very substantial increase in the amount
of transgene expression (up to 100-fold) could be achieved from rAAV
vectors by including essential bacterial plasmid elements in an upstream
intron. This could present substantial advantages for future in vivo