One-step synthesis of cationic steroids for gene delivery, anti-inflammatory activity, and antimicrobial activity.
Reagents for improved DNA lipofection, depot anti-inflammation, and/or topical antimicrobial therapy
Researchers in the Diamond Lab have developed a versatile new class of pharmacologically-active molecules with multiple applications. These molecules deliver plasmids (pDNA), adenovirus (AdV), and adeno-associated virus (AAV) to cultured cells and to pulmonary epithelium in vivo. In addition to their gene delivery capabilities, the structure of the molecules allows them to function as slow-release prodrugs for local treatment of vector-associated inflammation. Importantly, this therapeutic effect may synergize with the gene that is delivered.
The anti-inflammatory effect of the cationic steroids does not require DNA, and as the prodrugs degrade, they break down into non-toxic materials with pharmacological activity. The molecules can be readily synthesized in one-step from inexpensive precursors in a scalable reaction and purified in gram quantities. Additionally, the cationic steroids have potent antimicrobial activity against gram-positive and gram-negative bacteria, including clinical strains of MRSA and pseudomonas.
- Efficient delivery of genes to cultured cells
- Synergistic combination of gene delivery and anti-inflammatory effects to enhance gene therapy
- Rapid production of compound in large quantities
- Potent and rapid bactericidal activity against drug-resistant bacteria
- Gene therapy via non-viral gene delivery
- Slow-release therapeutics for treatment of inflammation
- Enhancer of DNA vaccines
- Pulmonary infections
Synthesis of a cationic steroid for gene delivery and anti-inflammatory activity. From Gruneich et al, 2004.
Stage of Development:
Proof-of-concept and mouse in vivo data