Scientists at the Polytechnic Institute of New York University (NYU-Poly) and the NYU College of Dentistry (NYUCD) report the development of a carrier that is five times more efficient in delivering DNA into cells than today's commercial reagent vector delivery methods. The new system is a peptide-polymer hybrid, assembled from two separate, less effective vectors that are used to carry DNA into cells.
Results of their study, “Long Term Efficient Gene Delivery Using Polyethylenimine with Modified Tat Peptide,” were published in Biomaterials. The findings were the result of a collaborative research project conducted by Seiichi Yamano, Ph.D., at NYUCD and Jin Montclare, Ph.D., at NYU-Poly. The outcome of the study could help researchers better understand gene function and ultimately improve gene therapy, according to Drs. Yamano and Montclare.
“Polyethylenimine (PEI), a cationic polymer, has been widely studied and shown great promise as an efficient gene delivery vehicle. Likewise, the HIV-1 Tat peptide, a cell-permeable peptide, has been successfully used for intracellular gene delivery,” wrote the investigators in their journal article. “To improve the favorable properties of these two vectors, we combine PEI with the modified Tat peptide sequence bearing histidine and cysteine residues (mTat). In vitro mTat/PEI-mediated transfection was evaluated by luciferase expression plasmid in two cell types. mTat/PEI produced significant improvement (≈5-fold) in transfection efficiency of both cell lines with little cytotoxicity when compared to mTat alone, PEI alone, or four commercial reagents.”
Traditionally, scientists have engineered viruses to carry out transfection, but viruses are problematic because cells recognize them as foreign and trigger the immune response. Virus transfection is extremely costly and presents numerous difficulties for mass processing.
On the other hand, nonviral vectors do not trigger the immune system and are easily manufactured and modified for safe, more effective delivery. Their shortcoming is that they generally are effective only for short periods in transfection, as well as other forms of gene expression. However, Drs. Yamano and Montclare tested their reagent vector both in vitro as well as for approximately seven months in vivo.
They say the vector may be used in the future for targeted gene therapy.