Our Dual Lentiviral Vector Delivery Platform

Using ex vivo and in vivo technologies to switch gene targets and create novel therapies for a broad range of genetic diseases.

Castle Creek Biosciences, a late-stage cell and gene therapy company, is utilizing a lentiviral vector (LV) delivery platform of ex vivo and in vivo technologies as the foundation to develop and commercialize novel therapies for genetic diseases. This versatile platform positions us to pursue multiple indications and accelerate expansion of our development pipeline by tailoring our therapeutic approach for the unique needs of each target indication.  

Castle Creek is experienced in using a self-inactivating (SIN) LV for developing an ex vivo gene therapy for the treatment of dystrophic epidermolysis bullosa (DEB), a progressive, devastatingly painful and debilitating, rare genetic disorder. LV can accommodate gene constructs and affect target cells by integrating the therapeutic genetic payload into the genome of these cells.1

Now, we are developing in vivo gene therapy programs, initially to address inborn errors of metabolism in the liver—starting with our lead program for hereditary tyrosinemia (HT1), which results from fumarylacetoacetate hydrolase (FAH) deficiency. Foundational preclinical research2 has shown that in vivo genetic correction of HT1 has the potential to be a precedent-setting approach2,3 for a broad range of therapeutic areas for underserved patient populations.4

Our Diversified Approach

1L Naldini 1, U Blömer, P Gallay, D Ory, R Mulligan, F H Gage, I M Verma, D Trono. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science. 1996 Apr 12; 272(5259):263-7. doi: 10.1126/science.272.5259.263 PMID: 8602510 DOI:10.1126/science.272.5259.263

2Clara T Nicolas, Caitlin J VanLith, Kari L Allen, Raymond D Hickey, Zeji Du, Lori G Hillin, Rebekah M Guthman, William J Cao, Aditya Bhagwate, Daniel O’Brien, Jean-Pierre Kocher, Robert A Kaiser, Stephen J Russell, Joseph B Lillegard. In vivo lentiviral vector gene therapy to cure hereditary tyrosinemia type 1 and prevent development of precancerous and cancerous lesions. bioRxiv 2021.01.02.425079; doi:

3Kaiser RA, Nicolas CT, Allen KL, Chilton JA, Du Z, Hickey RD, Lillegard JB. Hepatotoxicity and Toxicology of In Vivo Lentiviral Vector Administration in Healthy and Liver-Injury Mouse Models. Hum Gene Ther Clin Dev. 2019 Jun;30(2):57-66. doi: 10.1089/humc.2018.249. Epub 2019 Apr 11. PMID: 30860398; PMCID: PMC6589498.

4The future of gene-targeted therapy for hereditary tyrosinemia type 1 as a lead indication among the inborn errors of metabolism. Expert Opin Orphan Drugs. 2020;8(7):245-256. doi: 10.1080/21678707.2020.1791082. Epub 2020 Jul 21. PMID:33224636; PMCID: PMC7676758.)

Castle Creek Biosciences’ product candidates are investigational. None of our investigational gene therapies have received marketing approval by the U.S. Food and Drug Administration nor any other regulatory agency.