Goal of the Drug Discovery, Development and Delivery Core
The goal of the Penn State Skin Diseases Research Program is to foster novel innovative research in cancer and non-cancer related skin disease. To accomplish this objective, the Drug Discovery, Delivery and Development Core, provides Program investigators with access to technological expertise enabling RNAi & drug screening, organic compound & derivative analog synthesis, liposomal-based agent delivery and ultrasound technology for skin permeabalization. Thus, providing access to technologies enabling rapid identification of previously unidentified skin disease causing genes and agents to target these proteins to more effectively treat ailments.
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Activities of the Core
The Core will:
- Enable Core Program members to gain gain access to these technological capabilities by: assisting investigators in regulating gene expression in cells constituting skin, which includes; fibroblasts, keratinocytes and melanocytes, using siRNA to better understand skin diseases and identify proteins important in skin disorders.
- Provide Core Program investigators with access to siRNA and small molecule drug libraries as well as technological expertise to undertake drug screens to identify novel proteins regulating skin diseases and new agents effective for treating these disorders; enabling Core Program members to utilize liposomal technology to load siRNA or small molecule drugs to more effectively deliver these agents into skin to treat skin diseases.
- Allow Core Program investigators to utilize ultrasound technology to premeabalize skin in order to more efficiently deliver drug agents so as to effectively treat skin diseases.
Aims of the Drug Discovery, Delivery and Development Core
Aim 1: To provide screening of siRNA libraries in order to identify new proteins relevant to skin diseases.
Aim 2: To provide screening of a Natural Product Library for compounds to treat skin diseases.
Aim 3: To assist investigators in design of liposomal delivery vehicles for siRNAs and small molecules that can be used with and without ultrasound technology.
Aim 4: To synthesize compounds identified in screens or to modify existing compounds of interest to improve efficacy for treating skin diseases.
Aim 5: To provide detailed training to assist investigators in development of assays, design of siRNAs, and selection of delivery vehicles.
Services provided by the Core:
1. Drug Screening
The Drug Libraries:
The Drug, Discovery, Development and Delivery Core has available a 50,000 compound library from Chembridge. The DIVERSet of compounds were selected by Chembridge using druglike and desirable chemical group filters as well as 3D pharmacophore diversity analysis in order to provide a diverse set of druglike compounds. The library is provided in 96 well format at a concentration of 5mg/ml with the first and last columns containing DMSO as a control.
The core also has available a 480 compound Natural Product Library from TimTec. The library is provided in 96 well format at a concentration of 100 or 500 uM, with the first and last column of each plate left blank for user defined controls. The library is composed of naturally occurring compounds.
Library | # plates (96 well) | Base Cost* |
50,000 DIVERSet | 625 | $5643.75 |
Natural Product Library (480) | 6 | $135 |
*Base costs of libraries include 96 well plates and pipet tips for addition of compounds to wells.
Other consumables will be charged separately.
2. siRNA Screening
The siRNA libraries:
The Drug Discovery, Development, and Delivery Core has available eight libraries from Invitrogen. Each library has three separate siRNAs for each gene in the collection. Primary screening is done with each of the three siRNAs combined into one reaction. The single siRNAs can be used for confirmation in a secondary screen. The libraries are arrayed on 96 well plates. Each plate has the following controls, low, medium, high GC scrambled siRNAs, p53 siRNA, and fluorescent siRNA.
The core provides the nucleofection kit, tips and 96 well plates. The investigator is responsible for media, and reagents for screening. The core will perform the nucleofection and the screen.
Library | # plates (96 well) | Base Cost* |
siRNA Kinase (636) | 7.95 | $3722.96 |
siRNA Phosphastase (237) | 2.9625 | $1396.11 |
siRNA Nuclear Receptor (48) | 0.6 | $465.37 |
siRNA Nuclear Receptor Cofactor (280) | 3.5 | $1861.48 |
siRNA Ion Channel (326) | 4.075 | $2326.85 |
siRNA Non-olfactory GPCR (412) | 5.15 | $2792.22 |
siRNA Protease (366) | 4.575 | $2326.85 |
siRNA Ubiquitin Protease (53) | 0.6625 | $465.37 |
*Base Cost includes the nucleofection plate, tips, and three 96 well tissue culture plates.
Nucleofection:
The core uses Amaxa’s nucleofection technology for screening of siRNA libraries. Nucleofection is an electroporation method that introduces siRNA/plasmids into the nucleus of cells. In order to use nucleofection an appropriate nucleofection program must be selected. This can be done either by looking up your cell line on Amaxa’s website (
www.amaxa.com). Make sure the program number is for the 96 well shuttle system. If your cell line is not present in Amaxa ‘s database, Amaxa sells a nucleofector optimization kit that can be used to choose the correct program.
Nucleofection reagents | Cost ($) |
96 well kits | $422.40 per plate |
96 well optimization kit | $660 per cell line |
single cuvette kits | $15.27 per cuvette |
cuvette opitmization | $16.32 per cuvette |
Contact Details:
Dr. Melissa A Tran, Ph.D., Director: Drug Discovery, Delivery and Development Core
Telephone: 717-531-0003 ext 285888
