scholarly journals Association with Amino Acids Does Not Enhance Efficacy of Polymerized Liposomes As a System for Lung Gene Delivery

2016 ◽  
Vol 7 ◽  
Author(s):  
Elga Bandeira ◽  
Miquéias Lopes-Pacheco ◽  
Nadia Chiaramoni ◽  
Débora Ferreira ◽  
Maria J. Fernandez-Ruocco ◽  
...  
Keyword(s):  
Amino Acids ◽  
Gene Delivery ◽  
Polymerized Liposomes

Amino acids functionalized dendrimers with nucleus accumulation for efficient gene delivery

2021 ◽  
pp. 120641
Author(s):  
Guoxin Tan ◽  
Jiayang Li ◽  
Dandan Liu ◽  
Hao Pan ◽  
Renfang Zhu ◽  
...  
Keyword(s):  
Amino Acids ◽  
Gene Delivery ◽  
Efficient Gene

Structurally Mapping Antigenic Epitopes of Adeno-Associated Virus 9: Development of Antibody Escape Variants

2021 ◽  
Author(s):  
Shanan N. Emmanuel ◽  
J. Kennon Smith ◽  
Jane Hsi ◽  
Yu-Shan Tseng ◽  
Matias Kaplan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Monoclonal Antibodies ◽  
Gene Delivery ◽  
General Population ◽  
Neutralizing Antibodies ◽  
Rational Design ◽  
Transduction Efficiency ◽  
Viral Neutralization ◽  
Patient Cohort ◽  
Antigenic Epitopes

Adeno-associated viruses (AAV) serve as vectors for therapeutic gene delivery. AAV9 vectors have been FDA approved, as Zolgensma®, for the treatment of spinal muscular atrophy and is being evaluated in clinical trials for the treatment of neurotropic and musculotropic diseases. A major hurdle for AAV-mediated gene delivery is the presence of pre-existing neutralizing antibodies in 40 to 80% of the general population. These pre-existing antibodies can reduce therapeutic efficacy through viral neutralization, and the size of the patient cohort eligible for treatment. In this study, cryo-electron microscopy and image reconstruction was used to define the epitopes of five anti-AAV9 monoclonal antibodies (MAbs); ADK9, HL2368, HL2370, HL2372, and HL2374, on the capsid surface. Three of these, ADK9, HL2370, and HL2374, bound on or near the icosahedral 3-fold axes, HL2368 to the 2/5-fold wall, and HL2372 to the region surrounding the 5-fold axes. Pseudo-atomic modeling enabled the mapping and identification of antibody contact amino acids on the capsid, including S454 and P659. These epitopes overlap with previously defined parvovirus antigenic sites. Capsid amino acids critical for the interactions were confirmed by mutagenesis followed by biochemical assays testing recombinant AAV9 (rAAV9) variants capable of escaping recognition and neutralization by the parental MAbs. These variants retained parental tropism and had similar or improved transduction efficiency compared to AAV9. These engineered rAAV9 variants could expand the patient cohort eligible for AAV9-mediated gene delivery by avoiding pre-existing circulating neutralizing antibodies. IMPORTANCE The use of recombinant AAVs (rAAVs) as delivery vectors for therapeutic genes is becoming increasingly popular, especially following the FDA approval of Luxturna® and Zolgensma®, based on serotypes AAV2 and AAV9, respectively. However, high titer anti-AAV neutralizing antibodies in the general population, exempts patients from treatment. The goal of this study is to circumvent this issue by creating AAV variant vectors not recognized by pre-existing neutralizing antibodies. The mapping of the antigenic epitopes of five different monoclonal antibodies (MAbs) on AAV9, to recapitulate a polyclonal response, enabled the rational design of escape variants with minimal disruption to cell tropism and gene expression. This study, which included four newly developed and now commercially available MAbs, provides a platform for the engineering of rAAV9 vectors that can be used to deliver genes to patients with pre-exiting AAV antibodies.

Synergistic effect of amino acids modified on dendrimer surface in gene delivery

Biomaterials ◽  
2014 ◽  
Vol 35 (33) ◽  
pp. 9187-9198 ◽  
Author(s):  
Fei Wang ◽  
Yitong Wang ◽  
Hui Wang ◽  
Naimin Shao ◽  
Yuanyuan Chen ◽  
...  
Keyword(s):  
Amino Acids ◽  
Gene Delivery ◽  
Synergistic Effect

Charge-switching amino acids-based cationic lipids for efficient gene delivery

2015 ◽  
Vol 25 (24) ◽  
pp. 5677-5681 ◽  
Author(s):  
Li-Ting Zheng ◽  
Wen-Jing Yi ◽  
Qiang Liu ◽  
Rong-Chuan Su ◽  
Zhi-Gang Zhao
Keyword(s):  
Amino Acids ◽  
Gene Delivery ◽  
Cationic Lipids ◽  
Efficient Gene

scholarly journals Amino Acids, Peptides, and Proteins: Implications for Nanotechnological Applications in Biosensing and Drug/Gene Delivery

Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3002
Author(s):  
Simge Er ◽  
Ushna Laraib ◽  
Rabia Arshad ◽  
Saman Sargazi ◽  
Abbas Rahdar ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Amino Acids ◽  
Amino Acid ◽  
Gene Delivery ◽  
Cost Effective ◽  
Delivery Systems ◽  
Drug Molecules ◽  
Or Gene ◽  
Gold Nanoislands ◽  
Proteins And Peptides

Over various scientific fields in biochemistry, amino acids have been highlighted in research works. Protein, peptide- and amino acid-based drug delivery systems have proficiently transformed nanotechnology via immense flexibility in their features for attaching various drug molecules and biodegradable polymers. In this regard, novel nanostructures including carbon nanotubes, electrospun carbon nanofibers, gold nanoislands, and metal-based nanoparticles have been introduced as nanosensors for accurate detection of these organic compounds. These nanostructures can bind the biological receptor to the sensor surface and increase the surface area of the working electrode, significantly enhancing the biosensor performance. Interestingly, protein-based nanocarriers have also emerged as useful drug and gene delivery platforms. This is important since, despite recent advancements, there are still biological barriers and other obstacles limiting gene and drug delivery efficacy. Currently available strategies for gene therapy are not cost-effective, and they do not deliver the genetic cargo effectively to target sites. With rapid advancements in nanotechnology, novel gene delivery systems are introduced as nonviral vectors such as protein, peptide, and amino acid-based nanostructures. These nano-based delivery platforms can be tailored into functional transformation using proteins and peptides ligands based nanocarriers, usually overexpressed in the specified diseases. The purpose of this review is to shed light on traditional and nanotechnology-based methods to detect amino acids, peptides, and proteins. Furthermore, new insights into the potential of amino protein-based nanoassemblies for targeted drug delivery or gene transfer are presented.

Peptide-grafted dextran vectors for efficient and high-loading gene delivery

2019 ◽  
Vol 7 (4) ◽  
pp. 1543-1553 ◽  
Author(s):  
Yang Hu ◽  
Huifeng Wang ◽  
Haiqing Song ◽  
Megan Young ◽  
Yaqian Fan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Gene Delivery ◽  
Building Blocks ◽  
Delivery Systems ◽  
High Loading ◽  
Structure And Properties ◽  
Unique Structure ◽  
Polymeric Gene Delivery

Among various polymeric gene delivery systems, peptide-based vectors demonstrate great potential owing to their unique structure and properties, including flexibility; however, there is insufficient molecular understanding of the role and properties of amino acids as building blocks in gene delivery.

Preparation and gene delivery of alkaline amino acids-based cationic liposomes

2008 ◽  
Vol 31 (7) ◽  
pp. 924-931 ◽  
Author(s):  
Li Li ◽  
Yu Nie ◽  
Rong Zhu ◽  
Sanjun Shi ◽  
Kui Luo ◽  
...  
Keyword(s):  
Amino Acids ◽  
Gene Delivery ◽  
Cationic Liposomes

Homochirality as the Signature of Extra-Terrestrial Life

1997 ◽  
Vol 161 ◽  
pp. 505-510
Author(s):  
Alexandra J. MacDermott ◽  
Laurence D. Barron ◽  
Andrè Brack ◽  
Thomas Buhse ◽  
John R. Cronin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Optical Rotation ◽  
Physical Origin ◽  
Natural Choice ◽  
Rosetta Mission ◽  
Terrestrial Life ◽  
Subsurface Layers ◽  
Solar System Bodies ◽  
Origin Of Homochirality

AbstractThe most characteristic hallmark of life is its homochirality: all biomolecules are usually of one hand, e.g. on Earth life uses only L-amino acids for protein synthesis and not their D mirror images. We therefore suggest that a search for extra-terrestrial life can be approached as a Search for Extra- Terrestrial Homochirality (SETH). The natural choice for a SETH instrument is optical rotation, and we describe a novel miniaturized space polarimeter, called the SETH Cigar, which could be used to detect optical rotation as the homochiral signature of life on other planets. Moving parts are avoided by replacing the normal rotating polarizer by multiple fixed polarizers at different angles as in the eye of the bee. We believe that homochirality may be found in the subsurface layers on Mars as a relic of extinct life, and on other solar system bodies as a sign of advanced pre-biotic chemistry. We discuss the chiral GC-MS planned for the Roland lander of the Rosetta mission to a comet and conclude with theories of the physical origin of homochirality.

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