Biomedical subjects

Volker Patzel

Publications and source records attributed to Volker Patzel.

4 recordsLinked to original sources

PubMed2006

RNA Silencing in the struggle against disease.

Numerous acquired and hereditary diseases are caused by aberrant cellular or microbial gene expression. As a result of sequencing of the human genome and the genomes of various human pathogens, researchers have gained access to a large number of genes with residual functions. For functional validation of unknown genes, their functions can be specifically inhibited by antisense nucleic acids or small interfering RNAs (siRNAs) and the consequences of the functional loss, that is, the resulting phenotypes, can be analyzed. While antisense nucleic acids block the translation stoichiometrically by docking on the mRNA, siRNAs induce a highly effective cellular mechanism that causes catalytic destruction of several mRNA molecules by a single siRNA molecule. This mechanism, called RNA interference (RNAi), is only intrinsic to eukaryotic cells. Consequently, only eukaryotic target validation is pushed by RNAi whereas time-consuming conventional knockout techniques or the less efficient antisense strategies have to be applied for prokaryotic target validation. We succeeded in triggering gene silencing by siRNA in prokaryotic cells. This opens promising perspectives regarding validation of prokaryotic gene functions.

Genome, Bacterial↗

PubMed2005

Design of siRNAs producing unstructured guide-RNAs results in improved RNA interference efficiency.

In RNA interference (RNAi), guide RNAs direct RNA-induced silencing complexes (RISC) to their mRNA targets, thus enabling the cleavage that leads to gene silencing. We describe a strong inverse correlation between the degree of guide-RNA secondary structure formation and gene silencing by small interfering (si)RNA. Unstructured guide strands mediate the strongest silencing whereas structures with base-paired ends are inactive. Thus, the availability of terminal nucleotides within guide structures determines the strength of silencing. A to G and C to U base exchanges, which involve wobble base-pairing with the target but preserve complementarity, turned inactive into active guide structures, thereby expanding the space of functional siRNAs. Previously observed base degenerations among mature micro (mi)RNAs together with the data presented here suggest a crucial role of the guide-RNA structures in miRNA action. The analysis of the effect of the secondary structures of guide-RNA sequences on RNAi efficiency provides a basis for better understanding RNA silencing pathways and improving the design of siRNAs.

Algorithms↗

PubMed2004

In silico selection of functional RNA molecules.

Ribonucleic acid (RNA) molecules combine the coding potential of deoxyribonucleic acid (DNA) with various outwardly visible functions. RNA can be considered as a molecular unit of genotype and phenotype, and this concept has led to the hypothesis of a prebiotic world entirely dominated by RNA. In the postbiotic world, RNA is involved in all of the vital steps of information transfer from genes to gene products, and might intervene in gene expression and many other biological functions, either positively or negatively. RNA molecules have demonstrated tremendous potential as drug targets and drug candidates in the pharmaceutical and biotechnology industries, and are key components in a number of important processes, including microarray-based transcriptome analyses, functional target validation using antisense nucleic acids or short-interfering RNA (siRNA), and RNA-based drug development. The success of these significant but costly processes depends upon intelligent functional RNA design and the development of high-throughput compatible in silico selection tools and filters.

Animals↗

PubMed2003

Towards simple artificial infectious systems.

Inefficient gene delivery represents a major obstacle for widespread use of promising approaches in molecular medicine, including human gene therapy, genetic vaccination and gene suppression based on endogenous transcription of antisense RNA, ribozymes or small interfering RNA. We introduce a new concept of gene delivery by exploiting protein transduction. We discuss the feasibility of coupling intercellular spreading of phenotypes and their encoding genotypes in vivo, thus ensuring a compartmental linkage of genes of interest and their gene products, and thereby approaching an artificial infectious system. Such a system can be reduced to a few molecular components, and, hence, contrast with current gene delivery approaches, which incline to higher complexity. Artificial infectious systems can be useful for successive and penetrative tissue targeting.

Animals↗