PiggyBac Transposon System for Reprogramming Somatic Cells to Induced Pluripotent Stem (iPS) Cells.
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Current reprogramming strategies commonly utilize viral infection or plasmid transfection for the delivery of reprogramming factor transgenes. Although these methods are useful, they have several deficiencies. Viral reprogramming methods require multiple viral vector insertions which increase the risk of unintended genetic mutations, possibly resulting in cells with the potential to cause cancer. Plasmid reprogramming methods are transient and inefficient at reprogramming. Recently, a DNA transposon called piggyBac (PB) has demonstrated its ability to reprogram human fibroblast cells resulting in iPS cells with robust expression of pluripotency markers that can be used successfully in stringent differentiation assays. One major advantage of the piggyBac reprogramming system is its ability to be removed seamlessly from the genome after reprogramming has been completed, leaving no genetic footprint as if the insertion had never occurred.
Advantages of piggyBac
• PiggyBac exhibits stable expression in a large number of human and mammalian somatic cells (4, 5), whereas viral vectors are limited to cell types which are susceptible to infection (6). In fact, the PB system will likely integrate in any vertebrate cell line.
• PiggyBac can carry a large transgene cargo. PB has successfully delivered transgenes into the genome of 10-15 kb in length (7). In unpublished data, PB has demonstrated a delivery capacity of over 50 kb. The PB system can also be designed to deliver multiple transgenes to the same locus.
• PiggyBac exhibits no insertion preference within 50 kb of known proto-oncogenes (8). Viral vectors have been shown to integrate frequently near oncogenes, thereby stimulating expression and occasionally resulting in the development of leukemia or myelodysplasia (9).
• PiggyBac reprogramming methods require simple and inexpensive plasmids and transfection products, eliminating the need for biohazard containment facilities for virus production (6).
Transposagen Biopharmaceuticals, Inc. is the exclusive licensee of piggyBac for all human therapeutic applications and is actively seeking sublicensees for the use of piggyBac in the field of use of induced pluripotent stem (iPS) cells.
Please contact Jack Crawford if you are interested in a license: jcrawford@transposagenbio.com
