CPP-ZFN: A potential DNA-targeting anti-malarial drug
Abstract Background Multidrug-resistant Plasmodium is of major concern today. Effective vaccines or successful applications of RNAi-based strategies for the treatment of malaria are currently unavailable. An unexplored area in the field of malaria research is the development of DNA-targeting drugs t...
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ftdoajarticles:oai:doaj.org/article:c8f4fd70466841768842dcfa3071d497 2023-05-15T15:15:36+02:00 CPP-ZFN: A potential DNA-targeting anti-malarial drug Nain Vikrant Sahi Shakti Verma Anju 2010-09-01T00:00:00Z https://doi.org/10.1186/1475-2875-9-258 https://doaj.org/article/c8f4fd70466841768842dcfa3071d497 EN eng BMC http://www.malariajournal.com/content/9/1/258 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-9-258 1475-2875 https://doaj.org/article/c8f4fd70466841768842dcfa3071d497 Malaria Journal, Vol 9, Iss 1, p 258 (2010) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2010 ftdoajarticles https://doi.org/10.1186/1475-2875-9-258 2022-12-30T21:41:10Z Abstract Background Multidrug-resistant Plasmodium is of major concern today. Effective vaccines or successful applications of RNAi-based strategies for the treatment of malaria are currently unavailable. An unexplored area in the field of malaria research is the development of DNA-targeting drugs that can specifically interact with parasitic DNA and introduce deleterious changes, leading to loss of vital genome function and parasite death. Presentation of the hypothesis Advances in the development of zinc finger nuclease (ZFN) with engineered DNA recognition domains allow us to design and develop nuclease of high target sequence specificity with a mega recognition site that typically occurs only once in the genome. Moreover, cell-penetrating peptides (CPP) can cross the cell plasma membrane and deliver conjugated protein, nucleic acid, or any other cargo to the cytoplasm, nucleus, or mitochondria. This article proposes that a drug from the combination of the CPP and ZFN systems can effectively enter the intracellular parasite, introduce deleterious changes in its genome, and eliminate the parasite from the infected cells. Testing the hypothesis Availability of a DNA-binding motif for more than 45 triplets and its modular nature, with freedom to change number of fingers in a ZFN, makes development of customized ZFN against diverse target DNA sequence of any gene feasible. Since the Plasmodium genome is highly AT rich, there is considerable sequence site diversity even for the structurally and functionally conserved enzymes between Plasmodium and humans. CPP can be used to deliver ZFN to the intracellular nucleus of the parasite. Signal-peptide-based heterologous protein translocation to Plasmodium -infected RBCs (iRBCs) and different Plasmodium organelles have been achieved. With successful fusion of CPP with mitochondrial- and nuclear-targeting peptides, fusion of CPP with 1 more Plasmodium cell membrane translocation peptide seems achievable. Implications of the hypothesis Targeting of the Plasmodium genome ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Triplets ENVELOPE(-59.750,-59.750,-62.383,-62.383) Malaria Journal 9 1 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Nain Vikrant Sahi Shakti Verma Anju CPP-ZFN: A potential DNA-targeting anti-malarial drug |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Multidrug-resistant Plasmodium is of major concern today. Effective vaccines or successful applications of RNAi-based strategies for the treatment of malaria are currently unavailable. An unexplored area in the field of malaria research is the development of DNA-targeting drugs that can specifically interact with parasitic DNA and introduce deleterious changes, leading to loss of vital genome function and parasite death. Presentation of the hypothesis Advances in the development of zinc finger nuclease (ZFN) with engineered DNA recognition domains allow us to design and develop nuclease of high target sequence specificity with a mega recognition site that typically occurs only once in the genome. Moreover, cell-penetrating peptides (CPP) can cross the cell plasma membrane and deliver conjugated protein, nucleic acid, or any other cargo to the cytoplasm, nucleus, or mitochondria. This article proposes that a drug from the combination of the CPP and ZFN systems can effectively enter the intracellular parasite, introduce deleterious changes in its genome, and eliminate the parasite from the infected cells. Testing the hypothesis Availability of a DNA-binding motif for more than 45 triplets and its modular nature, with freedom to change number of fingers in a ZFN, makes development of customized ZFN against diverse target DNA sequence of any gene feasible. Since the Plasmodium genome is highly AT rich, there is considerable sequence site diversity even for the structurally and functionally conserved enzymes between Plasmodium and humans. CPP can be used to deliver ZFN to the intracellular nucleus of the parasite. Signal-peptide-based heterologous protein translocation to Plasmodium -infected RBCs (iRBCs) and different Plasmodium organelles have been achieved. With successful fusion of CPP with mitochondrial- and nuclear-targeting peptides, fusion of CPP with 1 more Plasmodium cell membrane translocation peptide seems achievable. Implications of the hypothesis Targeting of the Plasmodium genome ... |
format |
Article in Journal/Newspaper |
author |
Nain Vikrant Sahi Shakti Verma Anju |
author_facet |
Nain Vikrant Sahi Shakti Verma Anju |
author_sort |
Nain Vikrant |
title |
CPP-ZFN: A potential DNA-targeting anti-malarial drug |
title_short |
CPP-ZFN: A potential DNA-targeting anti-malarial drug |
title_full |
CPP-ZFN: A potential DNA-targeting anti-malarial drug |
title_fullStr |
CPP-ZFN: A potential DNA-targeting anti-malarial drug |
title_full_unstemmed |
CPP-ZFN: A potential DNA-targeting anti-malarial drug |
title_sort |
cpp-zfn: a potential dna-targeting anti-malarial drug |
publisher |
BMC |
publishDate |
2010 |
url |
https://doi.org/10.1186/1475-2875-9-258 https://doaj.org/article/c8f4fd70466841768842dcfa3071d497 |
long_lat |
ENVELOPE(-59.750,-59.750,-62.383,-62.383) |
geographic |
Arctic Triplets |
geographic_facet |
Arctic Triplets |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 9, Iss 1, p 258 (2010) |
op_relation |
http://www.malariajournal.com/content/9/1/258 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-9-258 1475-2875 https://doaj.org/article/c8f4fd70466841768842dcfa3071d497 |
op_doi |
https://doi.org/10.1186/1475-2875-9-258 |
container_title |
Malaria Journal |
container_volume |
9 |
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1 |
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1766345970400886784 |