These included cell lines derived from patients with ataxia telangiectasia, Nijmegen breakage syndrome, Fanconi anemia, defective Artemis, DNA ligase I and DNA ligase IV, an immunodeficient patient with a defect in DNA double-strand break repair, and a patient diagnosed with xeroderma pigmentosum who, in addition, showed severe clinical sensitivity to ionizing radiation.
Cellular hypersensitivity was confirmed in vitro and attributed to the ataxia-telangiectasia (A-T) gene in cases I and II, a newly described defect in the DNA ligase 4 gene in case III, and a novel and as yet incompletely defined, molecular defect in case IV who presented with xeroderma pigmentosum (XP).
Treatment with T4N5 liposomes containing a DNA repair enzyme enhanced repair synthesis in both normal and xeroderma pigmentosum keratinocytes in an irradiation- and liposome-dose dependent manner.