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Article ; Online: Oncolytic herpes simplex viruses for the treatment of glioma and targeting glioblastoma stem-like cells.

Kardani, Kimia / Sanchez Gil, Judit / Rabkin, Samuel D

Frontiers in cellular and infection microbiology

2023 Volume 13, Page(s) 1206111

Abstract: Glioblastoma (GBM) is one of the most lethal cancers, having a poor prognosis and a median survival of only about 15 months with standard treatment (surgery, radiation, and chemotherapy), which has not been significantly extended in decades. GBM ... ...

Abstract	Glioblastoma (GBM) is one of the most lethal cancers, having a poor prognosis and a median survival of only about 15 months with standard treatment (surgery, radiation, and chemotherapy), which has not been significantly extended in decades. GBM demonstrates remarkable cellular heterogeneity, with glioblastoma stem-like cells (GSCs) at the apex. GSCs are a subpopulation of GBM cells that possess the ability to self-renew, differentiate, initiate tumor formation, and manipulate the tumor microenvironment (TME). GSCs are no longer considered a static population of cells with specific markers but are quite flexible phenotypically and in driving tumor heterogeneity and therapeutic resistance. In light of these features, they are a critical target for successful GBM therapy. Oncolytic viruses, in particular oncolytic herpes simplex viruses (oHSVs), have many attributes for therapy and are promising agents to target GSCs. oHSVs are genetically-engineered to selectively replicate in and kill cancer cells, including GSCs, but not normal cells. Moreover, oHSV can induce anti-tumor immune responses and synergize with other therapies, such as chemotherapy, DNA repair inhibitors, and immune checkpoint inhibitors, to potentiate treatment effects and reduce GSC populations that are partly responsible for chemo- and radio-resistance. Herein, we present an overview of GSCs, activity of different oHSVs, clinical trial results, and combination strategies to enhance efficacy, including therapeutic arming of oHSV. Throughout, the therapeutic focus will be on GSCs and studies specifically targeting these cells. Recent clinical trials and approval of oHSV G47Δ in Japan for patients with recurrent glioma demonstrate the efficacy and promise of oHSV therapy.
MeSH term(s)	Humans ; Glioblastoma/drug therapy ; Glioblastoma/pathology ; Simplexvirus/genetics ; Oncolytic Virotherapy/methods ; Brain Neoplasms/drug therapy ; Brain Neoplasms/pathology ; Neoplasm Recurrence, Local/therapy ; Tumor Microenvironment
Language	English
Publishing date	2023-05-31
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2023.1206111
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Article ; Online: Antimicrobial/anticancer peptides: bioactive molecules and therapeutic agents.

Kardani, Kimia / Bolhassani, Azam

Immunotherapy

2021 Volume 13, Issue 8, Page(s) 669–684

Abstract: Antimicrobial peptides (AMPs) have been known as host-defense peptides. These cationic and amphipathic peptides are relatively short (∼5-50 L-amino acids) with molecular weight less than 10 kDa. AMPs have various roles including immunomodulatory, ... ...

Abstract	Antimicrobial peptides (AMPs) have been known as host-defense peptides. These cationic and amphipathic peptides are relatively short (∼5-50 L-amino acids) with molecular weight less than 10 kDa. AMPs have various roles including immunomodulatory, angiogenic and antitumor activities. Anticancer peptides (ACPs) are a main subset of AMPs as a novel therapeutic approach against tumor cells. The physicochemical properties of the ACPs influence their cell penetration, stability and efficiency of targeting. Up to now, several databases and web servers for
MeSH term(s)	Animals ; Antimicrobial Peptides ; Humans ; Neoplasms
Chemical Substances	Antimicrobial Peptides
Language	English
Publishing date	2021-04-21
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2495964-9
ISSN	1750-7448 ; 1750-743X
ISSN (online)	1750-7448
ISSN	1750-743X
DOI	10.2217/imt-2020-0312
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Article ; Online: Exploring novel and potent cell penetrating peptides in the proteome of SARS-COV-2 using bioinformatics approaches.

Kardani, Kimia / Bolhassani, Azam

PloS one

2021 Volume 16, Issue 2, Page(s) e0247396

Abstract: Among various delivery systems for vaccine and drug delivery, cell-penetrating peptides (CPPs) have been known as a potent delivery system because of their capability to penetrate cell membranes and deliver some types of cargoes into cells. Several CPPs ... ...

Abstract	Among various delivery systems for vaccine and drug delivery, cell-penetrating peptides (CPPs) have been known as a potent delivery system because of their capability to penetrate cell membranes and deliver some types of cargoes into cells. Several CPPs were found in the proteome of viruses such as Tat originated from human immunodeficiency virus-1 (HIV-1), and VP22 derived from herpes simplex virus-1 (HSV-1). In the current study, a wide-range of CPPs was identified in the proteome of SARS-CoV-2, a new member of coronaviruses family, using in silico analyses. These CPPs may play a main role for high penetration of virus into cells and infection of host. At first, we submitted the proteome of SARS-CoV-2 to CellPPD web server that resulted in a huge number of CPPs with ten residues in length. Afterward, we submitted the predicted CPPs to C2Pred web server for evaluation of the probability of each peptide. Then, the uptake efficiency of each peptide was investigated using CPPred-RF and MLCPP web servers. Next, the physicochemical properties of the predicted CPPs including net charge, theoretical isoelectric point (pI), amphipathicity, molecular weight, and water solubility were calculated using protparam and pepcalc tools. In addition, the probability of membrane binding potential and cellular localization of each CPP were estimated by Boman index using APD3 web server, D factor, and TMHMM web server. On the other hand, the immunogenicity, toxicity, allergenicity, hemolytic potency, and half-life of CPPs were predicted using various web servers. Finally, the tertiary structure and the helical wheel projection of some CPPs were predicted by PEP-FOLD3 and Heliquest web servers, respectively. These CPPs were divided into: a) CPP containing tumor homing motif (RGD) and/or tumor penetrating motif (RXXR); b) CPP with the highest Boman index; c) CPP with high half-life (~100 hour) in mammalian cells, and d) CPP with +5.00 net charge. Based on the results, we found a large number of novel CPPs with various features. Some of these CPPs possess tumor-specific motifs which can be evaluated in cancer therapy. Furthermore, the novel and potent CPPs derived from SARS-CoV-2 may be used alone or conjugated to some sequences such as nuclear localization sequence (NLS) for vaccine and drug delivery.
MeSH term(s)	Animals ; COVID-19 ; COVID-19 Vaccines/chemistry ; COVID-19 Vaccines/genetics ; COVID-19 Vaccines/metabolism ; Cell-Penetrating Peptides/chemistry ; Cell-Penetrating Peptides/genetics ; Cell-Penetrating Peptides/metabolism ; Computational Biology ; Computer Simulation ; Drug Delivery Systems ; HIV-1/chemistry ; HIV-1/genetics ; Herpesvirus 1, Human/chemistry ; Herpesvirus 1, Human/genetics ; Humans ; Proteome ; SARS-CoV-2/chemistry ; SARS-CoV-2/genetics ; SARS-CoV-2/metabolism ; Viral Structural Proteins/chemistry ; Viral Structural Proteins/genetics ; tat Gene Products, Human Immunodeficiency Virus/chemistry ; tat Gene Products, Human Immunodeficiency Virus/genetics
Chemical Substances	COVID-19 Vaccines ; Cell-Penetrating Peptides ; Proteome ; Viral Structural Proteins ; herpes simplex virus type 1 protein VP22 ; tat Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2021-02-19
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0247396
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Article: Cppsite 2.0: An Available Database of Experimentally Validated Cell-Penetrating Peptides Predicting their Secondary and Tertiary Structures

Kardani, Kimia / Bolhassani, Azam

Journal of molecular biology. 2021 May 28, v. 433, no. 11

2021

Abstract: One of the biggest barriers in drug and vaccine development is to find an effective delivery system. Cell-penetrating peptides (CPPs) play a crucial role for delivery of biological cargoes and pass them through the membranes. Several databases have been ... ...

Abstract	One of the biggest barriers in drug and vaccine development is to find an effective delivery system. Cell-penetrating peptides (CPPs) play a crucial role for delivery of biological cargoes and pass them through the membranes. Several databases have been developed for therapeutic peptides as potential drug candidates and delivery vehicles. A rapid growth has occurred in many patents and research articles on CPPs as therapeutic peptides. To save time and cost in laboratories, prediction and design of CPPs before in vitro/in vivo experiments using computational methods and online web servers are rational. Various online web servers which provide prediction of CPPs including CellPPD, CPPpred, CPPred-RF and MLCPP, and also different curated databases that present validated information of CPPs such as CPPsite 2.0 have been developed up to now. Two methods including CellPPD and CPPpred were applied to predict and design potent CPPs. CPPsite 2.0 is a user-friendly updated database that provides various information about CPPs and contains 1855 entries. This database provides comprehensive information on experimentally tested CPPs and prediction of their secondary and tertiary structures to realize their structure–function relationship. Furthermore, each entry presents information of a CPP including chirality, origin, nature of peptide, sub-cellular localization, uptake mechanism and efficiency, amino acid composition, hydrophobicity, and physicochemical properties. One of main goals of CPPsite 2.0 database is to provide the latest datasets of CPPs for analysis and development of CPP prediction methods. CPPsite 2.0 is freely available at https://webs.iiitd.edu.in/raghava/cppsite.
Keywords	amino acid composition ; data collection ; databases ; drugs ; hydrophobicity ; molecular biology ; optical isomerism ; peptides ; prediction ; structure-activity relationships ; therapeutics ; vaccine development
Language	English
Dates of publication	2021-0528
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2020.11.002
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Article ; Online: Exploring novel and potent cell penetrating peptides in the proteome of SARS-COV-2 using bioinformatics approaches.

Kimia Kardani / Azam Bolhassani

PLoS ONE, Vol 16, Iss 2, p e

2021 Volume 0247396

Abstract	Among various delivery systems for vaccine and drug delivery, cell-penetrating peptides (CPPs) have been known as a potent delivery system because of their capability to penetrate cell membranes and deliver some types of cargoes into cells. Several CPPs were found in the proteome of viruses such as Tat originated from human immunodeficiency virus-1 (HIV-1), and VP22 derived from herpes simplex virus-1 (HSV-1). In the current study, a wide-range of CPPs was identified in the proteome of SARS-CoV-2, a new member of coronaviruses family, using in silico analyses. These CPPs may play a main role for high penetration of virus into cells and infection of host. At first, we submitted the proteome of SARS-CoV-2 to CellPPD web server that resulted in a huge number of CPPs with ten residues in length. Afterward, we submitted the predicted CPPs to C2Pred web server for evaluation of the probability of each peptide. Then, the uptake efficiency of each peptide was investigated using CPPred-RF and MLCPP web servers. Next, the physicochemical properties of the predicted CPPs including net charge, theoretical isoelectric point (pI), amphipathicity, molecular weight, and water solubility were calculated using protparam and pepcalc tools. In addition, the probability of membrane binding potential and cellular localization of each CPP were estimated by Boman index using APD3 web server, D factor, and TMHMM web server. On the other hand, the immunogenicity, toxicity, allergenicity, hemolytic potency, and half-life of CPPs were predicted using various web servers. Finally, the tertiary structure and the helical wheel projection of some CPPs were predicted by PEP-FOLD3 and Heliquest web servers, respectively. These CPPs were divided into: a) CPP containing tumor homing motif (RGD) and/or tumor penetrating motif (RXXR); b) CPP with the highest Boman index; c) CPP with high half-life (~100 hour) in mammalian cells, and d) CPP with +5.00 net charge. Based on the results, we found a large number of novel CPPs with various features. Some of these CPPs possess tumor-specific motifs which can be evaluated in cancer therapy. Furthermore, the novel and potent CPPs derived from SARS-CoV-2 may be used alone or conjugated to some sequences such as nuclear localization sequence (NLS) for vaccine and drug delivery.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article: Gene delivery in adherent and suspension cells using the combined physical methods.

Kardani, Kimia / Milani, Alireza / Bolhassani, Azam

Cytotechnology

2022 Volume 74, Issue 2, Page(s) 245–257

Abstract: Physical methods are widely utilized to deliver nucleic acids into cells such as electro-transfection or heat shock. An efficient gene electro-transfection requires the best conditions including voltage, the pulse length or number, buffer, incubation ... ...

Abstract	Physical methods are widely utilized to deliver nucleic acids into cells such as electro-transfection or heat shock. An efficient gene electro-transfection requires the best conditions including voltage, the pulse length or number, buffer, incubation time and DNA form. In this study, the delivery of pEGFP-N1 vector into two adherent cell lines (HEK-293 T and COS-7) with the same origin (epithelial cells), and also mouse bone marrow-derived dendritic cells (DCs) was evaluated using electroporation under different conditions alone and along with heat treatment. Our data showed that the highest green fluorescent protein (GFP) expression in HEK-293 T and COS-7 cells was observed in serum-free RPMI cell culture medium as electroporation buffer, voltage (200 V), the pulse number (2), the pulse length (15 ms), the circular form of DNA, and 48 h after electro-transfection. In addition, the highest GFP expression in DCs was detected in serum-free RPMI, voltage (300 V), the pulse number (1), the pulse length (5 ms), and 48 h after electro-transfection. The use of sucrose as electroporation buffer, the pulse number (2), and the pulse length (25 ms) led to further cytotoxicity and lower transfection in HEK293T and COS-7 cells than other conditions. Moreover, the high voltage (700 V) increased the cell cytotoxicity, and decreased electro-transfection efficiency in DCs. On the other hand, the best conditions of electroporation along with heat treatment could significantly augment the transfection efficiency in all the cells. These data will be useful for gene delivery in other cells with the same properties using physical methods. Supplementary information: The online version contains supplementary material available at 10.1007/s10616-022-00524-4.
Language	English
Publishing date	2022-02-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	1035772-5
ISSN	0920-9069
ISSN	0920-9069
DOI	10.1007/s10616-022-00524-4
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Article ; Online: Cppsite 2.0: An Available Database of Experimentally Validated Cell-Penetrating Peptides Predicting their Secondary and Tertiary Structures.

Kardani, Kimia / Bolhassani, Azam

Journal of molecular biology

2020 Volume 433, Issue 11, Page(s) 166703

Abstract	One of the biggest barriers in drug and vaccine development is to find an effective delivery system. Cell-penetrating peptides (CPPs) play a crucial role for delivery of biological cargoes and pass them through the membranes. Several databases have been developed for therapeutic peptides as potential drug candidates and delivery vehicles. A rapid growth has occurred in many patents and research articles on CPPs as therapeutic peptides. To save time and cost in laboratories, prediction and design of CPPs before in vitro/in vivo experiments using computational methods and online web servers are rational. Various online web servers which provide prediction of CPPs including CellPPD, CPPpred, CPPred-RF and MLCPP, and also different curated databases that present validated information of CPPs such as CPPsite 2.0 have been developed up to now. Two methods including CellPPD and CPPpred were applied to predict and design potent CPPs. CPPsite 2.0 is a user-friendly updated database that provides various information about CPPs and contains 1855 entries. This database provides comprehensive information on experimentally tested CPPs and prediction of their secondary and tertiary structures to realize their structure-function relationship. Furthermore, each entry presents information of a CPP including chirality, origin, nature of peptide, sub-cellular localization, uptake mechanism and efficiency, amino acid composition, hydrophobicity, and physicochemical properties. One of main goals of CPPsite 2.0 database is to provide the latest datasets of CPPs for analysis and development of CPP prediction methods. CPPsite 2.0 is freely available at https://webs.iiitd.edu.in/raghava/cppsite.
MeSH term(s)	Cell-Penetrating Peptides/chemistry ; Computational Biology ; Databases, Protein ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Reproducibility of Results ; Software
Chemical Substances	Cell-Penetrating Peptides
Language	English
Publishing date	2020-11-10
Publishing country	England
Document type	Journal Article
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2020.11.002
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Article ; Online: The next generation of HCV vaccines: a focus on novel adjuvant development.

Kardani, Kimia / Sadat, Seyed Mehdi / Kardani, Mona / Bolhassani, Azam

Expert review of vaccines

2021 Volume 20, Issue 7, Page(s) 839–855

Abstract: Introduction: Considerable efforts have been made to treat and prevent acute and chronic infections caused by the hepatitis C virus (HCV). Current treatments are unable to protect people from reinfection. Hence, there is a need for development of both ... ...

Abstract	Introduction: Considerable efforts have been made to treat and prevent acute and chronic infections caused by the hepatitis C virus (HCV). Current treatments are unable to protect people from reinfection. Hence, there is a need for development of both preventive and therapeutic HCV vaccines. Many vaccine candidates are in development to fight against HCV, but their efficacy has so far proven limited partly due to low immunogenicity. Areas covered: We explore development of novel and powerful adjuvants to achieve an effective HCV vaccine. The basis for developing strong adjuvants is to understand the innate immunity pathway, which subsequently stimulates humoral and cellular immune responses. We have also investigated immunogenicity of developed adjuvants that have been used in recent studies available in online databases such as PubMed, PMC, ScienceDirect, Google Scholar, Expert opinion: Adjuvants are used as a part of vaccine formulation to boost vaccine immunogenicity and antigen delivery. Several FDA-approved adjuvants are used in licensed human vaccines. Unfortunately, no adjuvant has yet been proven to boost HCV immune responses to the extent needed for an effective vaccine. One of the promising approaches for developing an effective adjuvant is the combination of various adjuvants to trigger several innate immune responses, leading to activation of adaptive immunity.[Figure: see text].
MeSH term(s)	Adjuvants, Immunologic ; Hepacivirus ; Hepatitis C/prevention & control ; Humans ; Immunity, Cellular ; Vaccines
Chemical Substances	Adjuvants, Immunologic ; Vaccines
Language	English
Publishing date	2021-06-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2181284-6
ISSN	1744-8395 ; 1476-0584
ISSN (online)	1744-8395
ISSN	1476-0584
DOI	10.1080/14760584.2021.1941895
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Article ; Online: In Silico

Shabani, Samaneh H / Kardani, Kimia / Milani, Alireza / Bolhassani, Azam

Immunological investigations

2021 Volume 51, Issue 1, Page(s) 1–28

Abstract: In silico- ...

Abstract	In silico-
MeSH term(s)	AIDS Vaccines ; Animals ; Cell-Penetrating Peptides ; Epitopes, T-Lymphocyte ; HIV-1 ; Mice ; Molecular Docking Simulation ; rev Gene Products, Human Immunodeficiency Virus/immunology
Chemical Substances	AIDS Vaccines ; Cell-Penetrating Peptides ; Epitopes, T-Lymphocyte ; rev Gene Products, Human Immunodeficiency Virus ; rev protein, Human Immunodeficiency Virus-1
Language	English
Publishing date	2021-01-08
Publishing country	England
Document type	Journal Article
ZDB-ID	632565-8
ISSN	1532-4311 ; 0882-0139
ISSN (online)	1532-4311
ISSN	0882-0139
DOI	10.1080/08820139.2020.1867163
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Article ; Online: Antiviral therapy for the sexually transmitted viruses: recent updates on vaccine development.

Kardani, Kimia / Basimi, Parya / Fekri, Mehrshad / Bolhassani, Azam

Expert review of clinical pharmacology

2020 Volume 13, Issue 9, Page(s) 1001–1046

Abstract: Introduction: The sexually transmitted infections (STIs) caused by viruses including human T cell leukemia virus type-1 (HTLV-1), human immunodeficiency virus-1 (HIV-1), human simplex virus-2 (HSV-2), hepatitis C virus (HCV), hepatitis B virus (HBV), ... ...

Abstract	Introduction: The sexually transmitted infections (STIs) caused by viruses including human T cell leukemia virus type-1 (HTLV-1), human immunodeficiency virus-1 (HIV-1), human simplex virus-2 (HSV-2), hepatitis C virus (HCV), hepatitis B virus (HBV), and human papillomavirus (HPV) are major public health issues. These infections can cause cancer or result in long-term health problems. Due to high prevalence of STIs, a safe and effective vaccine is required to overcome these fatal viruses. Areas covered: This review includes a comprehensive overview of the literatures relevant to vaccine development against the sexually transmitted viruses (STVs) using PubMed and Sciencedirect electronic search engines. Herein, we discuss the efforts directed toward development of effective vaccines using different laboratory animal models including mice, guinea pig or non-human primates in preclinical trials, and human in clinical trials with different phases. Expert opinion: There is no effective FDA approved vaccine against the sexually transmitted viruses (STVs) except for HBV and HPV as prophylactic vaccines. Many attempts are underway to develop vaccines against these viruses. There are several approaches for improving prophylactic or therapeutic vaccines such as heterologous prime/boost immunization, delivery system, administration route, adjuvants,
MeSH term(s)	Animals ; Antiviral Agents/administration & dosage ; Disease Models, Animal ; Drug Development ; Guinea Pigs ; Humans ; Mice ; Primates ; Sexually Transmitted Diseases, Viral/drug therapy ; Sexually Transmitted Diseases, Viral/prevention & control ; Sexually Transmitted Diseases, Viral/virology ; Viral Vaccines/administration & dosage
Chemical Substances	Antiviral Agents ; Viral Vaccines
Language	English
Publishing date	2020-09-29
Publishing country	England
Document type	Journal Article ; Review
ISSN	1751-2441
ISSN (online)	1751-2441
DOI	10.1080/17512433.2020.1814743
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