Rutgers scientists have developed novel gold nanoparticles (AuNPs) functionalized with synthetic transcription factor (STF) components (AuSTF).
Rutgers scientists have developed novel gold nanoparticles (AuNPs) functionalized with synthetic transcription factor (STF) components (AuSTF) capable of permeating the plasma membrane, targeting and entering the nucleus, and initiating transcriptional activity of endogenous genes. STFs are comprised of synthetic small molecules and peptides, and can be potentially applied to investigate genome-wide transcriptional cascades, treat or repair malfunctioning signaling cascades within the cell, and guide differentiation or de-differentiation of cells into desired lineages. They also provide an attractive alternative to conventional retroviruses which randomly insert into the DNA genome and lead to the formation of teratomas.
Since its introduction over 15 years ago, advancement of STFs has faced significant challenges including poor membrane permeation, intracellular degradation, limited nuclear localization, low gene activation, and low synthesis efficiency. This technology utilizes AuNP (which are stable and non-toxic to cells) to tether STF components with the nuclear localization signal (NLS) peptides to help penetrate the nuclear membrane. The integration of AuNP with STF allows separate syntheses of different functional domains and tunable DNA-binding domain (DBD): activation domain (AD) ratio. The various components of the Au-STF can be further optimized to enhance gene regulation, modulate cytotoxicity and prevent intracellular degradation.
• Research tool for cellular gene expression modulation
• Gene therapy reagent to induce cellular reprogram-ming for the treatment of spinal cord injury, diabetes, cancer, wound healing, etc.
This technology is a versatile platform for modulation of gene expression at potent doses with:
Efficient membrane penetration
Precise gene targeting
Excellent stability and biocompatibility
Modification flexibility with additional targeting and enhancing moieties besides ST F domains
Ease of synthesis
Tunable DBD: AD ratio