Synthetic chromosomes

When a defective gene is replaced by a normal one, It will only help the individual receiving the treatment.

Germ line gene therapy is an approach that delivers genes to sperm or egg (or to the cells that produce them). It might prevent defective genes being transmitted to subsequent generation Gene modification at an early stage of embryonic development might also be a way of correcting gene defects in both the germ-line and body cells.

It is controversial because of its potential effect on future generations.Germ line gene therapy could potentially eliminate disease in future generations by repairing the original genetic defect in germ cells. However this therapy carries an unknown level of risk  (interference with another gene, specificity of the insertion). As a consequence germ line gene therapy is not being considered for application to humans at this time.

However if scientists could figure out how to make sure that a transferred gene goes into the cell's genome at the same position as the already mutated gene, then the safety of germ line gene therapy procedures might be dramatically increased.

           The technology of synthetic chromosomes is in that direction.

Recently, the magazine New Scientist (October 23, 1999) reported that  an artificial chromosome has been inserted into mice with success at a Canadian biotechnology company [Chromos Molecular Systems (Burnaby, British Columbia)]. It  was passed on its offspring. This positive result could revolutionize gene therapy (Canadian patent 2250682). "If genes could be ferried into embryosin an artificial chromosome, that could safely be inherited without interfering with the rest of the genome - the collection of all genes - germline therapy might not be so risky" (New Scientist).

Artificial chromosome makes engineering humans more temting than ever.

Athersis, Inc. (Cleveland, OH, U.S.A.) has developed a technology to create synthetic human microchromosomes (SMC). The synthetic micro chromosome is stable in dividing cells.

Chromosomes  must have three basic types of DNA. The first requirement is for DNA that encodes inherited genetic information. The second vital ingredient is telomeres, long strands of repeating DNA sequences that appear at the tips of chromosomes.  "The telomeres are the caps at the ends that keep the DNA from being eaten away, and which stop individual chromosomes from binding together, which would jumble the information" [H. Willard et al. Nature Genetics (1997) 15, 345]. The third requirement is centromeres, which provide the physical scaffolding that enables a duplicate chromosome to split from the original when cells divide. Like telomeres, centromeres consist of many repeats of the same short DNA sequence. (ref.: Human cells adopt DIY chromosome by Andy Coghlan  in: New Scientist, April 5, 1997).

The perspectives on the use of artificial chromosomes for gene therapy are reported on the article "Artificial Chromosomes Coming to Life" by Huntington F. Willard, on Science (2000) 290, 1308-1309. Questions related to telomeres, centromeres, stability of the artificial chromosome, alpha satellite sequences are illustrated, with a comment about the consideration of artificial human chromosomes as vectors for gene therapy.

Case Western Reserve University (CWRU)  (Cleveland, OH, U.S.A.) received a patent (N. 6,348,353 dated 02/19/2002) for the creation of an artificial chromosome, which can be used in gene therapy. CWRU is working with Athersis, Inc. (Cleveland, OH, U.S.A.)