Department of Dermatology and Cutaneous Biology and Department of Biochemistry and Molecular Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania, USA

Correspondence: Kyonggeun Yoon, Department of Dermatology and Cutaneous Biology and Department of Biochemistry and Molecular Pharmacology, Jefferson Medical College, 233 South 10th street, Philadelphia, Pennsylvania 19107, USA. Email: kyonggeun.yoon@jefferson.edu

Received 11 July 2003; Revised 11 July 2003; Accepted 29 October 2004.

Abstract

Oligonucleotide-directed gene alteration produces a targeted DNA sequence change in the genome of mammalian cells. The advantage of this approach is that expression of the corrected gene is regulated in the same way as a normal gene. Reliable, sensitive, and standardized assays played a critical role in the measurement of gene correction frequency among different cell types and in evaluating the structure–activity relationship of oligonucleotides. Mechanistic studies using these assays have become critical for understanding the gene repair process and setting realistic expectations on the capability of this technology. The epidermis is an ideal tissue where oligonucleotides can be administered locally and the treated sites can be monitored easily. But given the low frequency of gene correction, general selection procedures and amplification of corrected cells via epidermal stem cells are ultimately needed to make the gene repair technology practical. Recent data suggest that the in vivo application of oligonucleotides may be capable of gene correction in epidermal stem cells and the subsequent expansion of the corrected cells may result in an apparent high-level and long-lasting gene repair. Advances in oligonucleotide delivery and targeting of epidermal stem cells will be required for potential application of oligonucleotides toward treatment of genodermatoses.