Abstract: The invention pertains to an ex vivo method for increasing expression of at least one of gamma globin 1 (HBG1) and 2 (HBG2). The method can be used for the treatment or prevention of a haemoglobinopathy. The method comprises a step of introducing a first and a second site-specific endonuclease into a cell, wherein the first and second site-specific endonuclease generate a first and a second double stranded break in a chromosome, thereby generating a first, an intervening second and a third chromosomal fragment, wherein i) the first fragment comprises an beta globin locus control region (LCR) a functional fragment thereof; and ii) the third fragment comprises a sequence encoding at least one of HBG1 and HBG2. The length of the second intervening fragment is at least about 5 kb, and wherein joining the first fragment to the third fragment results in operably linking the beta globin LCR to the sequence encoding at least one of HBG1 and HBG2, thereby increasing at least one of HBG1 and HBG2 protein expression.

Abstract: The present invention relates to the field of molecular biology and more in particular to DNA technology. The invention relates to strategies for assessing structural integrity of DNA sequences of a genomic region of interest, which has clinical applications in diagnostics and personalized cancer therapy. In particular, the invention provides a method of detecting a chromosomal rearrangement involving a genomic region of interest.

Abstract: The current invention relates to strategies for selection and amplification of genomic regions of interest. The strategy involves an amplification step in a host cell. A target nucleotide sequence associated with the genomic region of interest is used to selectively provide a DNA circles derived from the genomic region of interest with an origin of replication and a selection gene. This is in particular useful i.a. for determining DNA sequences of a genomic region of interest, for use in building contiguous sequences and/or for DNA mapping.

Abstract: The invention relates to methods for determining the sequence of a genomic region of interest comprising a target nucleotide sequence comprising, fragmenting a crosslinked DNA, ligating the fragmented cross linked DNA, reversing the crosslinking and determining at least part of the sequences of ligated DNA fragments which comprise a target nucleotide sequence.