ABSTRACTS:

ARTICLE TITLE: REGULATED EXPRESSION OF ARTIFICIAL CHIMERIC GENES CONTAINED IN RETROVIRAL VECTORS: IMPLICATIONS FOR VIRUS-DIRECTED ENZYME PRODRUG THERAPY (VDEPT) AND OTHER GENE THERAPY APPLICATIONS.
AUTHOR: B.E. UBER BE, C.A. RICHARDS
JOURNAL: JOURNAL OF DRUG TARGETS 1996; 3(5):349-56
ABSTRACT: Replication-defective retroviral vectors were created that contained chimeric genes composed of human transcriptional regulatory sequences linked to the coding domain of a gene from Varicella zoster virus (VZV TK). These viruses were used to infect a human liver tumor cell line, HepG2.
After being infected, the infected liver cells were single-cell cloned. The level of expression of VZV TK from the chimeric genes correlated with the level of endogenous expression of the human genes in most clones, indicating that the transcription of the chimeric VZV TK gene is controlled in a similar manner to the human genes, and that sites of viral integration are less important to overall gene expression. Most importantly, as the expression of the human genes were modified, so was expression of VZV TK from the human/VZV TK chimeric gene. This demonstrates that retroviruses can deliver a chimeric gene containing tissue-specific transcriptional regulatory sequences that can respond to cell regulatory signals resulting in regulated gene expression.

KEY WORDS/PHRASES
CHIMERIC GENES
CLONED
CODING DOMAIN
ENDOGENOUS EXPRESSION
EXPRESSION
RETROVIRAL VECTORS
TRANSCRIPTION
TRANSCRIPTIONAL REGULATORY SEQUENCES
VIRAL INTEGRATION

ARTICLE TITLE: GENETIC CONFLICTS
AUTHOR: L.D.HURST, A.ATLAN, B.O. BENGTSSON
JOURNAL: QUARTERLY REVIEW OF BIOLOGY 1996 SEP; 71(3):317-64
ABSTRACT: Self-promoting elements (also called ultraselfish genes, selfish genes, or selfish genetic elements) are genetic entities that manipulate their "host" so as to promote their own spread, usually at a cost to other genes within the genome. The spread of a self-promoting element creates the need for the spread of a suppresser acting within the same genome. We may thus say that a genetic conflict exists between different components of the same genome. Here we investigate the properties of such conflicts.
First we consider the potential diversity of genomic conflicts and show that every genetic system has potential conflicts. This is followed by analysis of the logic of conflicts and by describing a distinction between competing and conflicting genes. Potential conflict in an unconstrained system can never be removed, and the course of evolution owing to conflict is often unpredictable. This is most particularly true for strong conflicts in which suppressers may take surprising forms. The possibility of extended conflicts in the form of "arms races" between element and suppresser is illustrated.
To illustrate, evolution conflict has been proposed as an important force in the development of sex, sex determination, species, recombination, and uniparental inheritance of cytoplasmic genes. In general, it is proposed that conflict may be a central force in the evolution of genetic systems. We conclude that an analysis of conflict and its general importance in evolution is greatly aided by application of the concept of genetic power. We consider the possible components of genetic power and ask whether and how power evolves.

KEY WORDS/PHRASES
EVOLUTION CONFLICT
GENETIC CONFLICT
GENETIC POWER
GENOME
SELF-PROMOTING ELEMENTS

ARTICLE TITLE: MAMMALIAN ARTIFICIAL CHROMOSOMES: A NEW TOOL FOR GENE THERAPY.
AUTHOR: C. HUXLEY
JOURNAL: GENE THERAPY, 1994 JAN; 1(1):7-12
ABSTRACT: Effective therapy by in vivo delivery of DNA requires efficient delivery, long-term maintenance of the DNA that is delivered and physiological levels of expression of the therapeutic gene. Full levels of physiologically controlled expression can be obtained after transfer of intact genes on fragments of DNA hundreds of kilobases in size, as has been demonstrated by the transfer of yeast artificial chromosomes into transgenic mice.
Long-term maintenance of input DNA could be achieved if the DNA carried replication origins, a centromere and telomeres to allow maintenance and segregation in mammalian cells, and there has been recent progress towards cloning these elements. These features could be combined as a mammalian artificial chromosome which would give full levels of controlled expression as well as being maintained in any cell into which it was introduced. Methods which would allow delivery of such large fragments of DNA include liposomes and receptor-mediated uptake, both of which have been shown to work in vivo, making such large constructs potentially possible for use in gene therapy.

KEY WORDS/PHRASES
CENTROMERE
CLONING
EXPRESSION
IN VIVO DELIVERY
LIPOSOMES
REPLICATION ORIGINS
TELOMERES
THERAPEUTIC GENE
TRANSGENIC
YEAST ARTIFICIAL CHROMOSOMES