抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics, have been the material of choice for many applications in regenerative medicine. They can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures, and serve as adhesives or barriers between tissue and material surfaces. In this work, the properties of hydrogels that are important for tissue engineering applications and the inherent material design constraints and challenges are discussed. Recent research involving several different hydrogels polymerized from a variety of synthetic and natural monomers using typical and novel synthetic methods are highlighted. Finally, special attention is given to the microfabrication techniques that are currently resulting in important advances in the field.

/pdf/hydrogels-in-regenerative-medicine-lx1cllc4g8.pdf

Hydrogels in regenerative medicine

https://dash.harvard.edu/bitstream/handle/1/29293165/Cancer%20Nanotechnology.pdf?sequence=1

Cancer Nanotechnology: The impact of passive and active targeting in the era of modern cancer biology

By exploiting the unique structural motifs and self-recognition properties of DNA, it is possible to generate self-assembled DNA nanostructures of specific shapes. Here, a previously described DNA 'origami' method has been extended into three dimensions to create an addressable DNA box on the nanometre scale that can be opened by an externally supplied DNA key'.

/pdf/self-assembly-of-a-nanoscale-dna-box-with-a-controllable-lid-4t0vka6sln.pdf

Self-assembly of a nanoscale DNA box with a controllable lid.

DNA molecules have been used to build a variety of nanoscale structures and devices over the past 30 years, and potential applications have begun to emerge. But the development of more advanced structures and applications will require a number of issues to be addressed, the most significant of which are the high cost of DNA and the high error rate of self-assembly. Here we examine the technical challenges in the field of structural DNA nanotechnology and outline some of the promising applications that could be developed if these hurdles can be overcome. In particular, we highlight the potential use of DNA nanostructures in molecular and cellular biophysics, as biomimetic systems, in energy transfer and photonics, and in diagnostics and therapeutics for human health.

/pdf/challenges-and-opportunities-for-structural-dna-32mi9330he.pdf

Challenges and opportunities for structural DNA nanotechnology

Genetic information storage and processing rely on just two polymers, DNA and RNA, yet whether their role reflects evolutionary history or fundamental functional constraints is currently unknown. With the use of polymerase evolution and design, we show that genetic information can be stored in and recovered from six alternative genetic polymers based on simple nucleic acid architectures not found in nature [xeno-nucleic acids (XNAs)]. We also select XNA aptamers, which bind their targets with high affinity and specificity, demonstrating that beyond heredity, specific XNAs have the capacity for Darwinian evolution and folding into defined structures. Thus, heredity and evolution, two hallmarks of life, are not limited to DNA and RNA but are likely to be emergent properties of polymers capable of information storage.

https://science.sciencemag.org/content/sci/336/6079/341.full.pdf

Synthetic genetic polymers capable of heredity and evolution

Aptamers are nucleic acid molecules that mimic antibodies by folding into complex 3D shapes that bind to specific targets. Although some aptamers exist naturally as the ligand-binding elements of riboswitches, most are generated in vitro and can be tailored for a specific target. Relative to antibodies, aptamers benefit from their ease of generation, low production cost, low batch-to-batch variability, reversible folding properties and low immunogenicity. However, the true value of aptamers lies in the simplicity by which these molecules can be engineered into sensors, actuators and other devices that are often central to emerging technologies. This Review examines changing trends in aptamer technology by analysing the first quarter century of aptamer data that is available in the scientific literature (1990–2015). We highlight specific examples that showcase the use of aptamers in key applications, discuss challenges that have impeded the success of aptamers in practical applications, provide suggestions for choosing chemical modifications that can lead to enhanced activity or stability, and propose standards for the characterization of aptamers in the scientific literature. Aptamers are nucleic acid molecules that can be evolved to bind to specific molecular targets and have found applications in technologies such as sensors and actuators. This Review provides a critical analysis of the first 25 years of aptamer research.

Analysis of aptamer discovery and technology

The pre-RNA world hypothesis postulates that RNA was preceded in the evolution of life by a simpler genetic material, but it is not known if such systems can fold into structures capable of eliciting a desired function. Presumably, whatever chemistry gave rise to RNA would have produced other RNA analogues, some of which may have preceded or competed directly with RNA. Threose nucleic acid (TNA), a potentially natural derivative of RNA, has received considerable interest as a possible RNA progenitor due to its chemical simplicity and ability to exchange genetic information with itself and RNA. Here, we have applied Darwinian evolution methods to evolve, in vitro, a TNA receptor that binds to an arbitrary target with high affinity and specificity. This demonstration shows that TNA has the ability to fold into tertiary structures with sophisticated chemical functions, which provides evidence that TNA could have served as an ancestral genetic system during an early stage of life.

Darwinian evolution of an alternative genetic system provides support for TNA as an RNA progenitor

In vitro selection coupled with directed evolution represents a powerful method for generating nucleic acids and proteins with desired functional properties. Creating high-quality libraries of random sequences is an important step in this process as it allows variants of individual molecules to be generated from a single-parent sequence. These libraries are then screened for individual molecules with interesting, and sometimes very rare, phenotypes. Here, we describe a general method to introduce random nucleotide mutations into a parent sequence that takes advantage of the polymerase chain reaction (PCR). This protocol reduces mutational bias often associated with error-prone PCR methods and allows the experimenter to control the degree of mutagenesis by controlling the number of gene-doubling events that occur in the PCR reaction. The error-prone PCR method described here was used to optimize a de novo evolved protein for improved folding stability, solubility, and ligand-binding affinity.

John C. Chaput

Papers

Synthetic genetic polymers capable of heredity and evolution

Analysis of aptamer discovery and technology

Darwinian evolution of an alternative genetic system provides support for TNA as an RNA progenitor

Random Mutagenesis by Error-Prone PCR

Self-assembled peptide nanoarrays: an approach to studying protein-protein interactions.