Chapter 15. Gene and Cell Therapy

Summary

More than 5,000 monogenic disorders have been linked to DNA alteration at a specific gene locus. Cell and gene therapy, although conceived primarily as a means to correct monogenic disorder, is now recognized also as a strategy with therapeutic potential for a wide range of acquired disorders including infections, neurological diseases, and cancers. Early examples of cell and gene therapy include bone marrow, organ, and tissue transplantation, where tissues and organs containing genetic information from the donor are transmitted to the recipient. While several definitions of cell and gene therapy have been advanced, a working definition includes embryonic cloning—generally known as animal and human cloning—via transfer of an engineered nucleus. Therefore, any strategy using nucleic acids—DNA or RNA derivatives—to treat, modify, or prevent a medical condition are considered as cell and gene therapy. Nucleic acids containing genetic information could act as inhibitors for gene expression. Anti-sense nucleic acid sequences designed to bind to target gene sequences and inhibit transcriptions, and ribozymes designed to degrade specific RNA transcripts, are also considered gene therapeutics.

The advances in genetic and cellular research have allowed development of cell and gene therapeutic strategies for treating wide-ranging medical conditions. The most common strategy is to use engineered nucleic acids that can be delivered to target cells and express functional protein. Some of the molecular designs of gene constructs and intricacies in gene delivery systems are discussed in detail in section 2 of this chapter. The field of gene therapy founded on molecular and cellular principles is still in its infancy and many technical and ethical issues are yet to be addressed. Although some cells and gene therapies have had limited success, efficiency and safety concerns must be addressed before they can be thought of as a mainstream therapeutic strategy.