Current Issues in Molecular Biology

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Open AccessReview

DNA Vaccine Delivery and Improved Immunogenicity

by Kevin R. Porter and Kanakatte Raviprakash

Curr. Issues Mol. Biol. 2017, 22(1), 129-138; https://doi.org/10.21775/cimb.022.129 - 11 Nov 2016

Cited by 53 | Viewed by 1882

The promise of DNA vaccines is as compelling today as it was more than a decade ago. Ease of manufacture, stability at ambient temperatures without the need for a cold chain and its ability to mimic natural infections and elicit appropriate immune responses [...] Read more.

The promise of DNA vaccines is as compelling today as it was more than a decade ago. Ease of manufacture, stability at ambient temperatures without the need for a cold chain and its ability to mimic natural infections and elicit appropriate immune responses makes this vaccine platform extremely attractive. Although, human clinical trials of DNA vaccines have yielded less than optimal results, the approval and licensing of a few veterinary vaccines is testimony to the proof-of-concept and the hope that licensed DNA vaccines for human use may not be too far away. Delivery and targeting of immunologically relevant cells appears to be the major hurdle in maximizing the immunogenicity of DNA vaccines. Several different approaches that are currently pursued in achieving this objective are discussed. Full article

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Open AccessReview

mRNA: A Versatile Molecule for Cancer Vaccines

by Mustafa Diken, Lena M. Kranz, Sebastian Kreiter and Ugur Sahin

Curr. Issues Mol. Biol. 2017, 22(1), 113-128; https://doi.org/10.21775/cimb.022.113 - 02 Nov 2016

Cited by 37 | Viewed by 1652

Abstract

mRNA vaccines are finally ready to assume their rightful place at the forefront of nucleic acid-based vaccines. Major achievements within the last two decades have turned this highly versatile molecule into a safe and very attractive pharmaceutical platform that combines many positive attributes [...] Read more.

mRNA vaccines are finally ready to assume their rightful place at the forefront of nucleic acid-based vaccines. Major achievements within the last two decades have turned this highly versatile molecule into a safe and very attractive pharmaceutical platform that combines many positive attributes able to address a broad range of diseases, including cancer. The simplicity of mRNA vaccines greatly reduces complications generally associated with the production of biological vaccines. Intrinsic costimulatory and inflammatory triggers in addition to the provision of the antigenic information makes mRNA an all-in-one molecule that does not need additional adjuvants and that does not pose the risk of genomic integration. Clinical studies in various cancer types are moving forward and promising results with favorable clinical outcome are awaited. This review will recapitulate conceptual, mechanistic and immune-related features of this highly versatile molecule, elucidate how these features have been addressed in the past, and how comprehensive understanding can foster further optimization for broad application possibilities in cancer treatment. Full article

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Open AccessReview

Genomics: A Hallmark to Monitor Molecular and Biochemical Processes Leading toward a Better Perceptive of Seed Aging and Ex-Situ Conservation

by Zaheer Ahmed, Zahid Hussain Shah, Hafiz Mamoon Rehman, Khurram Shahzad, Ihsanullah Daur, Abdalla Elfeel, Mahmood ul Hassan, Ali Khalid Elsafori, Seung Hwan Yang and Gyuhwa Chung

Curr. Issues Mol. Biol. 2017, 22(1), 89-112; https://doi.org/10.21775/cimb.022.089 - 02 Nov 2016

Cited by 9 | Viewed by 549

Abstract

For human food security, the preservation of 7.4 million ex-situ germplasm is a global priority. However, ex-situ-conserved seeds are subject to aging, which reduces their viability and ultimately results in the loss of valuable genetic material over long periods. Recent progress in seed [...] Read more.

For human food security, the preservation of 7.4 million ex-situ germplasm is a global priority. However, ex-situ-conserved seeds are subject to aging, which reduces their viability and ultimately results in the loss of valuable genetic material over long periods. Recent progress in seed biology and genomics has revealed new opportunities to improve the long-term storage of ex-situ seed germplasm. This review summarizes the recent improvements in seed physiology and genomics, with the intention of developing genomic tools for evaluating seed aging. Several lines of seed biology research have shown promise in retrieving viability signal from various stages of seed germination. We conclude that seed aging is associated with mitochondrial alteration and programmed cell death, DNA and enzyme repair, anti-oxidative genes, telomere length, and epigenetic regulation. Clearly, opportunities exist for observing seed aging for developing genomic tools to increment the traditional germination test for effective conservation of ex-situ germplasm. Full article

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Open AccessReview

DNA Vaccines: Regulatory Considerations and Safety Aspects

by Anne Ingeborg Myhr

Curr. Issues Mol. Biol. 2017, 22(1), 79-88; https://doi.org/10.21775/cimb.022.079 - 06 Oct 2016

Cited by 49 | Viewed by 1083

Abstract

DNA vaccines have great potential as preventive or therapeutic vaccines against viral, bacterial, or parasitic diseases as well as cancer, and may also be used as gene therapy products. Although many human and veterinary DNA vaccines have been investigated in laboratory trials, only [...] Read more.

DNA vaccines have great potential as preventive or therapeutic vaccines against viral, bacterial, or parasitic diseases as well as cancer, and may also be used as gene therapy products. Although many human and veterinary DNA vaccines have been investigated in laboratory trials, only four of these have been approved for commercial use. In this paper an overview of the regulatory requirements for the development of DNA vaccines is given. The regulatory process in EU and USA is described. A discussion concerning the relevance of national regulations on gene technology is included. In addition the main safety concerns associated with DNA vaccines, relating to unwanted side effects in the vaccinated mammal or fish, are presented. Finally, the need for greater openness regarding the assessment information is discussed. Full article

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Open AccessReview

Far from the Madding Crowd: The Molecular Basis for Immunological Escape of Plasmodium falciparum

by Manuel E. Patarroyo, Jorge Aza-Conde, Armando Moreno-Vranich, Laura Pabón, Yahson Varela and Manuel A. Patarroyo

Curr. Issues Mol. Biol. 2017, 22(1), 65-78; https://doi.org/10.21775/cimb.022.065 - 05 Oct 2016

Cited by 7 | Viewed by 334

Abstract

Like Thomas Hardy’s famous novel Far from the Madding Crowd, Plasmodium falciparum parasites display their most relevant survival structures (proteins) involved in host cell invasion far away from the immune system’s susceptible regions, displaying tremendous genetic variability, to attract the immune response and [...] Read more.

Like Thomas Hardy’s famous novel Far from the Madding Crowd, Plasmodium falciparum parasites display their most relevant survival structures (proteins) involved in host cell invasion far away from the immune system’s susceptible regions, displaying tremendous genetic variability, to attract the immune response and escape immune pressure. The 3D structure localisation of the conserved amino acid sequences of this deadly parasite’s most relevant proteins involved in host cell invasion, as well as the location of the highly polymorphic, highly immunogenic regions, clearly demonstrates that such structures are far apart, sometimes 90° to 180° opposite, thereby rendering the immune response useless. It is also shown here that these conserved, functionally-relevant structures are immunologically silent, since no immune response has been induce. Full article

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Open AccessReview

Liver X Receptors and Their Agonists: Targeting for Cholesterol Homeostasis and Cardiovascular Diseases

by Zhiqiang Ma, Chao Deng, Wei Hu, Jie Zhou, Chongxi Fan, Shouyin Di, Dong Liu, Yang Yang and Dongjin Wang

Curr. Issues Mol. Biol. 2017, 22(1), 41-64; https://doi.org/10.21775/cimb.022.041 - 28 Sep 2016

Cited by 66 | Viewed by 849

Abstract

Liver X receptors α (LXRα) and β (LXRβ) are essential for protection against cardiovascular diseases. LXRs are members of the nuclear receptor superfamily of DNA-binding transcription factors and act as sensors of cholesterol homeostasis. In this review, we introduce LXRs and briefly describe [...] Read more.

Liver X receptors α (LXRα) and β (LXRβ) are essential for protection against cardiovascular diseases. LXRs are members of the nuclear receptor superfamily of DNA-binding transcription factors and act as sensors of cholesterol homeostasis. In this review, we introduce LXRs and briefly describe the roles of LXRs in reverse cholesterol transport and trans-intestinal cholesterol efflux. We discuss LXR agonists and the downstream genes of LXRs that are involved in the regulation of cholesterol transport. In addition, we describe the cardioprotective effects of LXRs against atherosclerosis, myocardial ischemia/reperfusion injury, diabetic cardiomyopathy, and myocardial hypertrophy. Finally, we expand our discussion to the actions of LXRs in atherosclerosis and suggest several potential research avenues that may be of interest to clinicians and basic scientists. The information included herein may be useful for the design of future experimental research studies and may advance the investigation of LXRs as therapeutic targets. Full article

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Open AccessReview

Molecular Adjuvants for DNA Vaccines

by Lei Li and Nikolai Petrovsky

Curr. Issues Mol. Biol. 2017, 22(1), 17-40; https://doi.org/10.21775/cimb.022.017 - 21 Sep 2016

Cited by 52 | Viewed by 1451

Abstract

Poor immunogenicity remains the single biggest obstacle to human DNA vaccines achieving their potential. Strategies to improve DNA vaccine efficacy include codon optimization, transfection reagents, electroporation, vaccine adjuvants or combination with a protein or vector boost. Increased understanding of molecular events driving innate [...] Read more.

Poor immunogenicity remains the single biggest obstacle to human DNA vaccines achieving their potential. Strategies to improve DNA vaccine efficacy include codon optimization, transfection reagents, electroporation, vaccine adjuvants or combination with a protein or vector boost. Increased understanding of molecular events driving innate and adaptive immune responses has assisted development of molecular adjuvants for DNA vaccine use. Such adjuvants comprise plasmid-encoded signalling molecules including cytokines, chemokines, immune costimulatory molecules, toll-like receptor agonists or inhibitors of immune suppressive pathways. New approaches including gene knockdown, epigenetics and systems biology have also contributed to an increased range of molecular adjuvant options. This review explores current and future trends in vaccine design including the latest molecular adjuvants for enhanced DNA vaccine efficacy. Full article

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Open AccessReview

Systems Vaccinology Applied to DNA Vaccines: Perspective and Challenges

by Melissa Lever, Eduardo L. Silveira and Helder I. Nakaya

Curr. Issues Mol. Biol. 2017, 22(1), 1-16; https://doi.org/10.21775/cimb.022.001 - 21 Sep 2016

Cited by 5 | Viewed by 316

Abstract

DNA vaccination represents a new milestone in our technological efforts to avoid infectious diseases. Although this method of vaccination has had success in providing protection in animals, these vaccines suffer from low immunogenicity in humans. Questions remain over the molecular mechanism of DNA [...] Read more.

DNA vaccination represents a new milestone in our technological efforts to avoid infectious diseases. Although this method of vaccination has had success in providing protection in animals, these vaccines suffer from low immunogenicity in humans. Questions remain over the molecular mechanism of DNA vaccination, the best ways in which to safely increase vaccine reactogenecity, and what biomarkers can be used as correlates of protection. Systems vaccinology, which utilizes modern experimental and computational approaches to provide an integrated view of the vaccination process, offers the potential to answer these questions. In this review we discuss the current tools utilized in systems vaccinology, the ways in which they have and can be applied to DNA vaccinology, and challenges faced in the field. Full article

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Curr. Issues Mol. Biol., Volume 22, Issue 1 (April 2017) – 8 articles

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