Lifeboat Foundation

The remarkable physicochemical properties of the natural nucleic acids, DNA and RNA, define modern biology at the molecular level and are widely believed to have been central to life’s origins. However, their ability to form repositories of information as well as functional structures such as ligands (aptamers) and catalysts (ribozymes/DNAzymes) is not unique. A range of nonnatural alternatives, collectively termed xeno nucleic acids (XNAs), are also capable of supporting genetic information storage and propagation as well as evolution. This gives rise to a new field of “synthetic genetics,” which seeks to expand the nucleic acid chemical toolbox for applications in both biotechnology and molecular medicine. In this review, we outline XNA polymerase and reverse transcriptase engineering as a key enabling technology and summarize the application of “synthetic genetics” to the development of aptamers, enzymes, and nanostructures.

Copyright © 2019 Cold Spring Harbor Laboratory Press; all rights reserved.

How life emerged from simple non-life chemicals on the ancient Earth is one of the greatest mysteries in biology. The gene expression system of extant life is based on the interdependence between multiple molecular species (DNA, RNA, and proteins). While DNA is mainly used as genetic material and proteins as functional molecules in modern biology, RNA serves as both genetic material and enzymes (ribozymes). Thus, the evolution of life may have begun with the birth of a ribozyme that replicated itself (the RNA world hypothesis), and proteins and DNA joined later. However, the complete self-replication of ribozymes from monomeric substrates has not yet been demonstrated experimentally, due to their limited activity and stability. In contrast, peptides are more chemically stable and are considered to have existed on the ancient Earth, leading to the hypothesis of RNA-peptide co-evolution from the very beginning. Our group and collaborators recently demonstrated that peptides with both hydrophobic and cationic moieties (e.g., KKVVVVVV) form β-amyloid aggregates that adsorb RNA and enhance RNA synthesis by an artificial RNA polymerase ribozyme and a simple peptide with only seven amino acid types (especially rich in valine and lysine) can fold into the ancient β-barrel conserved in various enzymes, including the core of cellular RNA polymerases. These findings, together with recent reports from other groups, suggest that simple prebiotic peptides could have supported the ancient RNA-based replication system, gradually folded into RNA-binding proteins, and eventually evolved into complex proteins like RNA polymerase.

Keywords: RNA world; ancient proteins; central dogma; origin of life; peptide.

© 2023 Japanese Society of Developmental Biologists.

Individual RNA remains a challenging signal to synthetically transduce into different types of cellular information. Here, we describe Ribozyme-ENabled Detection of RNA (RENDR), a plug-and-play strategy that uses cellular transcripts to template the assembly of split ribozymes, triggering splicing reactions that generate orthogonal protein outputs. To identify split ribozymes that require templating for splicing, we use laboratory evolution to evaluate the activities of different split variants of the Tetrahymena thermophila ribozyme. The best design delivers a 93-fold dynamic range of splicing with RENDR controlling fluorescent protein production in response to an RNA input. We further resolve a thermodynamic model to guide RENDR design, show how input signals can be transduced into diverse outputs, demonstrate portability across different bacteria, and use RENDR to detect antibiotic-resistant bacteria. This work shows how transcriptional signals can be monitored in situ and converted into different types of biochemical information using RNA synthetic biology.

© 2023. The Author(s).

Conflict of interest statement.

Enzyme-catalyzed replication of nucleic acid sequences is a prerequisite for the survival and evolution of biological entities. Before the advent of protein synthesis, genetic information was most likely stored in and replicated by RNA. However, experimental systems for sustained RNA-dependent RNA-replication are difficult to realise, in part due to the high thermodynamic stability of duplex products and the low chemical stability of catalytic RNAs. Using a derivative of a group I intron as a model for an RNA replicase, we show that heated air-water interfaces that are exposed to a plausible CO₂-rich atmosphere enable sense and antisense RNA replication as well as template-dependent synthesis and catalysis of a functional ribozyme in a one-pot reaction. Both reactions are driven by autonomous oscillations in salt concentrations and pH, resulting from precipitation of acidified dew droplets, which transiently destabilise RNA duplexes. Our results suggest that an abundant Hadean microenvironment may have promoted both replication and synthesis of functional RNAs.

© 2023. The Author(s).

Conflict of interest statement.

Reported here are experiments that show that ribonucleoside triphosphates are converted to polyribonucleic acid when incubated with rock glasses similar to those likely present 4.3−4.4 billion years ago on the Hadean Earth surface, where they were formed by impacts and volcanism. This polyribonucleic acid averages 100–300 nucleotides in length, with a substantial fraction of 3’,-5’-dinucleotide linkages. Chemical analyses, including classical methods that were used to prove the structure of natural RNA, establish a polyribonucleic acid structure for these products. The polyribonucleic acid accumulated and was stable for months, with a synthesis rate of 2 × 10^-3 pmoles of triphosphate polymerized each hour per gram of glass (25°C, pH 7.5). These results suggest that polyribonucleotides were available to Hadean environments if triphosphates were. As many proposals are emerging describing how triphosphates might have been made on the Hadean Earth, the process observed here offers an important missing step in models for the prebiotic synthesis of RNA.

Keywords: Impact glasses; Mafic rocks; Nucleoside triphosphates; Origin of life; Prebiotic chemistry; RNA world.

Conflict of interest statement.

The team developed a cyclical process in which the device is rinsed with water, dried in relatively low heat, and printed on again.

In the electronics industry, placing several layers of components on top of each other to develop complex devices is no easy task. And with printed electronics, the task is more complicated.

“If you’re making a peanut butter and jelly sandwich, one layer on either slice of bread is easy,” Aaron Franklin, the Addy Professor of Electrical and Computer Engineering at Duke, said in a statement. “But if you put the jelly down first and then try to spread peanut butter on top of it, forget it, the jelly won’t stay put and will intermix with the peanut butter.

Continue reading “Researchers print fully recyclable electronics that replace toxic chemicals with water” »

Researchers have developed a new way to produce and shape large, high-quality mirrors that are much thinner than the primary mirrors previously used for telescopes deployed in space. The resulting mirrors are flexible enough to be rolled up and stored compactly inside a launch vehicle.

“Launching and deploying space telescopes is a complicated and costly procedure,” said Sebastian Rabien from Max Planck Institute for Extraterrestrial Physics in Germany. “This new approach—which is very different from typical mirror production and polishing procedures—could help solve weight and packaging issues for telescope mirrors, enabling much larger, and thus more sensitive, telescopes to be placed in orbit.”

In the journal Applied Optics, Rabien reports successful fabrication of parabolic membrane mirror prototypes up to 30 cm in diameter. These mirrors, which could be scaled up to the sizes needed in space telescopes, were created by using chemical vapor deposition to grow membrane mirrors on a rotating liquid inside a vacuum chamber. He also developed a method that uses heat to adaptively correct imperfections that might occur after the mirror is unfolded.

Materials that can conduct negatively charged hydrogen atoms in ambient conditions could pave the way for advanced clean energy storage and electrochemical conversion technologies. A research team from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) demonstrated a technique that enables a room-temperature all-solid-state hydride cell by introducing and exploiting defects in the lattice structure of rare earth hydrides. Their study was published in Nature on April 5.

Solid materials that conduct lithium, sodium and hydrogen cations have been used in batteries and fuel cells. Under certain conditions, some of the materials transition to superionic states where ions move as fast as they do in liquids by skipping through the rigid crystal structure. This phenomenon is advantageous for chemical and energy conversions as it allows ions to move without a liquid or soft membrane to separate the electrodes. However, few solid-state materials can reach this state under ambient conditions.

“Materials that exhibit superionic conduction at ambient conditions would provide huge opportunities for constructing brand new all-solid-state hydride batteries, fuel cells and electrochemical cells for the storage and conversion of clean energy,” said Prof. Chen Ping, study author from DICP.

^c Department of Chemical Biology, Xiamen University, Xiamen, 361,005, China.

The concept of xeno-nucleic acids (XNAs) was first proposed in 2009 in a theoretical paper, referring to additional types of nucleic acids, whose sugar moieties would differ from those in DNA and RNA. However, with the rising popularity of XNAs, the definition of XNAs has been extended to unnatural nucleic acids with chemically modified sugar, nucleobase, or phosphate moieties that are distinct from those found in DNA and RNA. The discovery and engineering of both polymerases and reverse transcriptases to synthesize, replicate and evolve a diverse range of XNAs has attracted significant attention and has enabled the discovery of XNA ligands (aptamers) and XNA catalysts (XNAzymes) as well as the synthesis of XNA nanostructures with potential as novel therapeutics. The field of XNAs continues to grow rapidly towards realizing the potential of XNAs in biotechnology and molecular medicine. This themed issue unites a collection of articles attesting to the rapid progress in the field.

One of the key advantages of XNAs is their generally enhanced resistance to nuclease degradation. This biostability, the affinity and specificity towards a target, and the general lack of immunogenicity of modified nucleic acids are critical for their potential application as therapeutics. Modified sugar moieties such as 2′-modified analogs, conformationally locked analogs, and threose-replaced analogs in particular contribute to the increased biological stability of XNAs against enzymatic degradation. Replacing the phosphodiester linkages with charge-neutral backbones including peptide-like backbones and triazole-linked backbones offers further opportunities to tune the stability, conformation and physicochemical properties of XNAs and enhance the affinity to their targets.