Delivering siRNA in vivo for functional genomics and novel therapeutics

2005 ◽  
pp. 303-317 ◽  
Author(s):  
Patrick Y. Lu ◽  
Martin C. Woodle
2004 ◽  
Vol 16 (2) ◽  
pp. 87 ◽  
Author(s):  
Le Ann Blomberg ◽  
Kurt A. Zuelke

Functional genomics provides a powerful means for delving into the molecular mechanisms involved in pre-implantation development of porcine embryos. High rates of embryonic mortality (30%), following either natural mating or artificial insemination, emphasise the need to improve the efficiency of reproduction in the pig. The poor success rate of live offspring from in vitro-manipulated pig embryos also hampers efforts to generate transgenic animals for biotechnology applications. Previous analysis of differential gene expression has demonstrated stage-specific gene expression for in vivo-derived embryos and altered gene expression for in vitro-derived embryos. However, the methods used to date examine relatively few genes simultaneously and, thus, provide an incomplete glimpse of the physiological role of these genes during embryogenesis. The present review will focus on two aspects of applying functional genomics research strategies for analysing the expression of genes during elongation of pig embryos between gestational day (D) 11 and D12. First, we compare and contrast current methodologies that are being used for gene discovery and expression analysis during pig embryo development. Second, we establish a paradigm for applying serial analysis of gene expression as a functional genomics tool to obtain preliminary information essential for discovering the physiological mechanisms by which distinct embryonic phenotypes are derived.


Toxins ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 421 ◽  
Author(s):  
Jonathan Davies ◽  
Sai Liu ◽  
K. Acharya

Botulinum neurotoxins (BoNTs) are categorised into immunologically distinct serotypes BoNT/A to /G). Each serotype can also be further divided into subtypes based on differences in amino acid sequence. BoNTs are ~150 kDa proteins comprised of three major functional domains: an N-terminal zinc metalloprotease light chain (LC), a translocation domain (HN), and a binding domain (HC). The HC is responsible for targeting the BoNT to the neuronal cell membrane, and each serotype has evolved to bind via different mechanisms to different target receptors. Most structural characterisations to date have focussed on the first identified subtype within each serotype (e.g., BoNT/A1). Subtype differences within BoNT serotypes can affect intoxication, displaying different botulism symptoms in vivo, and less emphasis has been placed on investigating these variants. This review outlines the receptors for each BoNT serotype and describes the basis for the highly specific targeting of neuronal cell membranes. Understanding receptor binding is of vital importance, not only for the generation of novel therapeutics but also for understanding how best to protect from intoxication.


2020 ◽  
Author(s):  
Xiphias Ge Zhu ◽  
Aleksey Chudnovskiy ◽  
Lou Baudrier ◽  
Benjamin Prizer ◽  
Yuyang Liu ◽  
...  

2020 ◽  
Vol 6 (12) ◽  
pp. 1002-1017
Author(s):  
Chennan Li ◽  
Andrea L. Kasinski
Keyword(s):  

2019 ◽  
Vol 3 (1) ◽  
pp. 345-363 ◽  
Author(s):  
Thomas A. O'Loughlin ◽  
Luke A. Gilbert

Functional genomics holds great promise for the dissection of cancer biology. The elucidation of genetic cooperation and molecular details that govern oncogenesis, metastasis, and response to therapy is made possible by robust technologies for perturbing gene function coupled to quantitative analysis of cancer phenotypes resulting from genetic or epigenetic perturbations. Multiplexed genetic perturbations enable the dissection of cooperative genetic lesions as well as the identification of synthetic lethal gene pairs that hold particular promise for constructing innovative cancer therapies. Lastly, functional genomics strategies enable the highly multiplexed in vivo analysis of genes that govern tumorigenesis as well as of the complex multicellular biology of a tumor, such as immune response and metastasis phenotypes. In this review, we discuss both historical and emerging functional genomics approaches and their impact on the cancer research landscape.


Neoplasia ◽  
2020 ◽  
Vol 22 (8) ◽  
pp. 294-310
Author(s):  
Suzie K. Hight ◽  
Allison Mootz ◽  
Rahul K. Kollipara ◽  
Elizabeth McMillan ◽  
Paul Yenerall ◽  
...  

2021 ◽  
Author(s):  
Feng Ding ◽  
Hongqian Zhang ◽  
Jiwei Cui ◽  
Qiang Li ◽  
Chuanxu Yang

In vitro transcribed messenger RNA (IVT-mRNA) holds great promise for the development of novel therapeutics, such as immunotherapy and vaccination. However, the main obstacle to clinical translation is the lack...


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