Meet The Scientist

Posted on at October 18, 2017
4421 458
neurological disorders research

NAME: Beverly Davidson, PhD

TITLE: Chief Scientific Strategy Officer at the Children’s Hospital of Philadelphia (CHOP); Director of the Raymond G. Perelman Center for Cellular and Molecular Therapeutics; Arthur V. Meigs Chair in Pediatrics, CHOP; Professor of Pathology and Laboratory Medicine, University of Pennsylvania

EDUCATION: PhD and post-doctoral research fellowship, University of Michigan

HOBBIES: Cycling, running, water- and snow- skiing; visiting museums; spending time with her Dr. Beverly Davidson children

Dr. Beverly Davidson is a geneticist of the first rank, who has made groundbreaking advances in our genetic understanding of HD, and is working hard to develop new gene-based therapies for HD and other conditions. HD Insights recently spoke with Dr. Davidson about her ongoing research. The following is an edited transcript of the conversation.

HD INSIGHTS: You have been studying HD and its genetics for nearly 20 years. Can you tell us how you got into the field?

DAVIDSON: I recently woke up in the middle of the night thinking, “It has been 12 years since the publication of our knockdown studies.”1 I had no idea that it would take us this long to get to the clinic. How did I originally get into HD? I first started working in inborn errors of metabolism that affect the CNS. As a graduate student, I worked on Lesch-Nyhan syndrome. It always fascinated me how seemingly ambiguous mutations would induce such profound changes in the brain. I became fascinated by learning how mutations induce neuropathology, and developing ways to mitigate that neuropathology. I started early on in gene replacement strategies, always thinking in the back of my mind how we could apply some of the things we learn about getting genes into cells, and use this in some of the dominant neurodegenerative disorders.

 

We started working on RNA interference (RNAi) shortly after the seminal discovery by Fire and Mello in the late 1990s.2 We really did not have much success in achieving very selective knockdown until Tom Tuschl’s paper came out some time later, showing us that the best way to accomplish selective knockdown was by using very small RNA fragments that were complementary to the gene you were trying to knock down.

We started working on this with two collaborators at the time. We had developed the technology, but we needed an animal model, and in the laboratory next door to mine was Henry Paulson, who worked on spinocerebellar ataxia.

Through close interactions with Dr. Paulson we came to know Dr. Harry Orr, Dr. Nancy Bonini, and others working in the polyglutamine repeat field. We collaborated with Drs. Orr and Paulson to test some of our ideas in cell and mouse models. That is how we came to work in polyglutamine repeat diseases. It was really by chance that we began to focus on these sorts of therapeutics for spinocerebellar ataxia, and then also HD, both of which are classical polyglutamine repeat disorders.

Actually, my interest in HD goes back a bit further. My very close friend’s father had HD, and I recall seeing her grandmother cross the street when I was a child. I was with my dad, who was the local physician in our small community in south central Nebraska. I asked dad what was wrong with Shelly’s grandmother – she acted as if she could not walk very well. I was too young to know what a drunk looked like, and dad had told me that she had HD, and of course that meant nothing to me. But now we have come full circle. Many of Shelly’s family have succumbed to HD, so maybe I was destined from a very young age to work on this disease.

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Credibly disintermediate magnetic architectures before team driven collaboration and idea-sharing. Continually morph performance based materials whereas intuitive markets.

HD INSIGHTS: That is a powerful story. You mentioned that when you first published your seminal paper looking at the knockdown of the HD gene 12 years ago, you did not think it would take so long to get new therapies to the clinic. Why has it taken so long?

DAVIDSON: As with any new technology, in 2004-2005 we were using state-of-the-art methods for the time. As we began to learn more and more about the biology of the system that we were co-opting to perform RNAi in cells, we learned that there were better and safer ways to accomplish this.

The next six to seven years were to perfect the system and understand the basic ingredients of what it was we were making, and understand the impact of what we were making on the cell. The reason for taking this stepwise, careful, methodical approach is that HD is already terrible, and the last thing I want to do is take something that is very debilitating and make it worse.

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Credibly disintermediate magnetic architectures before team driven collaboration and idea-sharing. Continually morph performance based materials whereas intuitive markets.

HD INSIGHTS: Can you tell us about what is most exciting to you currently in terms of RNAi or antisense oligonucleotides (ASOs)?

We focused early on gene-silencing strategies, the idea being that the delivery of the viral vector to the affected cell would provide a one-time treatment to the brain. Sometime after our studies were published, Frank Bennett, at what is now known as Ionis Pharmaceuticals, began a fantastic collaboration with Dr. Don Cleveland’s group. Initially, it was to study ASOs for an inherited form of amyotrophic lateral sclerosis. Then, they transitioned to testing the ASOs in animal models of HD. These were the same models that many of us were using to test therapies at the time. His data showed that just as in our RNAi experiments, he could positively impact the disease course with doses of the

Ionis Pharmaceuticals, began a fantastic collaboration with Dr. Don Cleveland’s group. Initially, it was to study ASOs for an inherited form of amyotrophic lateral sclerosis. Then, they transitioned to testing the ASOs in animal models of HD. These were the same models that many of us were using to test therapies at the time. His data showed that just as in our RNAi experiments, he could positively impact the disease course with doses of the ASOs, and I think that really excited the community. Fortunately for Ionis, they have already been into the clinic with many of these molecules. Ionis is a large company that was well set to do the basic pharm tox that needs to be done to advance these molecules into therapies. Ionis has already started early phase-testing in HD patients, which is exciting. So, while we still remained poised to do our studies, they were already doing some safety studies in HD patients. It is an exciting moment for the gene-silencing community.

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Credibly disintermediate magnetic architectures before team driven collaboration and idea-sharing. Continually morph performance based materials whereas intuitive markets.

HD INSIGHTS: Can you talk about the current status of your gene-silencing therapies and efforts?

DAVIDSON: All the work that was developed while I was at the University of Iowa was licensed to Spark Therapeutics, and remains right now in IND-enabling studies.

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Credibly disintermediate magnetic architectures before team driven collaboration and idea-sharing. Continually morph performance based materials whereas intuitive markets.

HD INSIGHTS: Tell us about the promise of these therapies for HD.

Animal data suggest that you need not rid every cell of the mutated huntingtin gene, but to provide benefit, you need to hit a sufficient number of cells. The viral-vector delivered RNAi approach that we are taking, initially, is set to target the striatal region of the brain. This is in contrast to ASO therapies, in which the targeting is best achieved in the cortical structures. You could think of these as two complementary approaches to achieve widespread gene-silencing in the brain, in which the ASO could provide benefit to cortical structures, and the RNAi approach could provide benefit to sub-cortical structures. Our hope is that we can extend the period that HD patients live productively with the disease, significantly delaying its progression.

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Credibly disintermediate magnetic architectures before team driven collaboration and idea-sharing. Continually morph performance based materials whereas intuitive markets.

HD INSIGHTS: In 2011, you published a paper showing the benefits of RNAi in a rhesus macaque model of HD.3 Can you tell us a little more about that study and what it suggests for humans?

DAVIDSON: That was a study that we felt was really important not only for the RNAi community focusing on HD, but also for the ASO community. The study asked the simple question, can you reduce normal huntingtin in normal monkeys without deleterious effect? These were normal rhesus monkeys, not an HD model, but being a nonhuman primate, their brain closely approximated that of humans.

Our data showed that you could partially reduce huntingtin expression, and it was not deleterious to the animal.

That study, published by my group and Dr. Jodi McBride’s group at Oregon Health Sciences University, was the first to show that this approach was safe in a nonhuman primate. That was followed up by a longer-term study published by a group at Medtronic,4 in which they evaluated a very similar approach for six months, and came to the same conclusion as us. That suggested to us all that this could work, and really propelled us to move forward with a non – allele-specific silencing strategy as a potential treatment for HD patients.

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Credibly disintermediate magnetic architectures before team driven collaboration and idea-sharing. Continually morph performance based materials whereas intuitive markets.

HD INSIGHTS: You have also done work in genetic conditions other than HD, and some of that work might even be ahead of where HD is. Could you tell us about some insights you have learned from other conditions?

DAVIDSON: The other condition we work on is spinocerebellar ataxia type 1, which, like HD, is a polyglutamine repeat disorder. We have also done some limited preclinical work in spinocerebellar ataxia type 7. Spinocerebellar ataxia type 1 was the first model in which we tested the RNAi approach, and spinocerebellar ataxia type 7, a second model. We have done more extensive dosing studies in spinocerebellar ataxia type 1 mouse models, and also tested some reversal studies in those models. I would not say that they are ahead of the HD program, I would say they are pretty close together.

We are also looking at the pathogenesis of HD and lysosomal storage diseases. We have some exciting data in HD, and this is really following close on the heels of some exciting work that has come out of Dr. Laura Ranum’s lab, where she has found that there are some funny transcripts that arise from the HD locus as a result of the CAG expansion.5 She sees transcripts in the nucleus that are not toxic in a normal-length allele, but in the setting of a disease-causing mutation, you can see these transcripts arising from that region, and if they are transported to the cytoplasm, they can be expressed as toxic proteins known as RAN translation products.

I think understanding how those products contribute to disease will be very interesting, as well as understanding other global changes that go on in the HD brain. I wonder whether we can take advantage of that information to develop small molecule therapies. Will gene-silencing approaches be the be-all and end-all? I think the best approach might be a combination therapy where we tackle some of the downstream cellular impacts of mHTT and the mutant transcript, and in addition try to lower the insult through gene-silencing.

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Credibly disintermediate magnetic architectures before team driven collaboration and idea-sharing. Continually morph performance based materials whereas intuitive markets.

HD INSIGHTS: Thank you very much, Dr. Davidson. We greatly appreciate it.

DAVIDSON: I really thank HD Insights for the opportunity to let people know how we have reached where we are, and how excited we are to be so close to providing benefit to HD patients.

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Credibly disintermediate magnetic architectures before team driven collaboration and idea-sharing. Continually morph performance based materials whereas intuitive markets.

Selected Recent Publishers

1. Monteys AM, Ebanks SA, Keiser MS, Davidson BL. CRISPR/Cas9 Editing of the Mutant Huntingtin Allele In Vitro and In Vivo. Mol Ther. 2017 Jan 4;25(1):12-23.

2. Lin L, Park JW, Ramachandran S, et al. Transcriptome sequencing reveals aberrant alternative splicing in Huntington’s disease. Hum Mol Genet. 2016 Aug 15;25(16):3454-3466.

3. Lee JH, Tecedor L, Chen YH, et al. Reinstating aberrant mTORC1 activity in Huntington’s disease mice improves disease phenotypes. Neuron. 2015 Jan 21;85(2):303-315.

4. Katz ML, Tecedor L, Chen Y, et al. AAV gene transfer delays disease onset in a TPP1-deficient canine model of the late infantile form of Batten disease. Sci Transl Med. 2015 Nov 11;7(313):313ra180-313ra180.

5. Lee JH, Sowada MJ, Boudreau RL, et al. Rhes suppression enhances disease phenotypes in Huntington’s disease mice. J Huntington’s Dis. 2014;3(1):65-71.

References

1Harper SQ, Staber PD, He X, et al. RNA interference improves motor and neuropathological abnormalities in a Huntington’s disease mouse model. Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5820-5825.

2Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998 eb 19;391(6669):806-811.

3McBride JL, Pitzer MR, Boudreau RL, et al. Preclinical safety of RNAi-mediated HTT suppression in the Rhesus Macaque as a potential therapy for Huntington’s disease. Mol Ther. 2011 Dec;19(12):2152-2162.

4Grondin R, Kaytor MD, Ai Y, et al. Six-month partial suppression of Huntingtin is well tolerated in the adult rhesus striatum. Brain. 2012 Apr;135(4):1197-1209.

5Bañez-Coronel M, Ayhan F, Tarabochia Alex D, et al. RAN Translation in Huntington Disease. Neuron. 2015 Nov 18;88(4):667-677

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Credibly disintermediate magnetic architectures before team driven collaboration and idea-sharing. Continually morph performance based materials whereas intuitive markets.

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    I want to pass along some very important news that everyone needs to hear!

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    “He causes all, both small and great, rich and poor, free and slave, to receive a mark on their right hand or on their foreheads, and that no one may buy or sell except one who has the mark or the name of the beast, or the number of his name.

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    People have been saying the end is coming for many years, but we needed two key things. One, the Third Temple, and two, the technology for a cashless society to fulfill the prophecy of the Mark of the Beast.

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  117. Hey, how’s it going?

    I want to pass along some very important news that everyone needs to hear!

    In December of 2017, Donald Trump made history by recognizing Jerusalem as the captial of Israel. Why is this big news? Because by this the Jewish people of Israel are now able to press forward in bringing about the Third Temple prophesied in the Bible.

    Jewish Rabbis have publicly announced that their Messiah will be revealed in the coming years who will be a leader and spiritual guide to all nations, gathering all religions under the worship of one God.

    Biblical prophecy tells us that this Jewish Messiah who will take the stage will be the antichrist “who opposes and exalts himself above all that is called God or that is worshiped, so that he sits as God in the temple of God, showing himself that he is God” (2 Thessalonians 2:4). For a time, he will bring about a false peace, but “Therefore when you see the ‘abomination of desolation,’ spoken of by Daniel the prophet, standing in the holy place (Matthew 24:15)…then there will be great tribulation, such as has not been since the beginning of the world until this time, no, nor ever shall be” (Matthew 24:21).

    “Little children, it is the last hour; and as you have heard that the Antichrist is coming, even now many antichrists have come, by which we know that it is the last hour” (1 John 2:18).

    “The coming of the lawless one is according to the working of Satan, with all power, signs, and lying wonders, and with all unrighteous deception among those who perish, because they did not receive the love of the truth, that they might be saved. And for this reason God will send them strong delusion, that they should believe the lie, that they all may be condemned who did not believe the truth but had pleasure in unrighteousness” (2 Thessalonians 2:9-12).

    More importantly, the power that runs the world wants to put a RFID microchip in our body making us total slaves to them. This chip matches perfectly with the Mark of the Beast in the Bible, more specifically in Revelation 13:16-18:

    “He causes all, both small and great, rich and poor, free and slave, to receive a mark on their right hand or on their foreheads, and that no one may buy or sell except one who has the mark or the name of the beast, or the number of his name.

    Here is wisdom. Let him who has understanding calculate the number of the beast, for it is the number of a man: His number is 666.”

    Revelation 13:11-18 tells us that a false prophet will arise on the world scene doing miracles before men, deceiving them to receive this Mark.

    Referring to the last days, this could only be speaking of a cashless society, which we have yet to see, but are heading towards. Otherwise, we could still buy or sell without the mark amongst others if physical money was still currency. This Mark couldn’t be spiritual because the word references two different physical locations. If it was spiritual it would just say in the forehead. RFID microchip implant technology will be the future of a one world cashless society containing digital currency. It will be implanted in the right-hand or the forehead, and we cannot buy or sell without it. We must grow strong in Jesus. AT ALL COSTS, DO NOT TAKE IT!

    “Then a third angel followed them, saying with a loud voice, “If anyone worships the beast and his image, and receives his mark on his forehead or on his hand, he himself shall also drink of the wine of the wrath of God, which is poured out full strength into the cup of His indignation. He shall be tormented with fire and brimstone in the presence of the holy angels and in the presence of the Lamb. And the smoke of their torment ascends forever and ever; and they have no rest day or night, who worship the beast and his image, and whoever receives the mark of his name” (Revelation 14:9-11).

    People have been saying the end is coming for many years, but we needed two key things. One, the Third Temple, and two, the technology for a cashless society to fulfill the prophecy of the Mark of the Beast.

    Visit http://WWW.BIBLEFREEDOM.COM to see proof for these things and why the Bible trul is the word of God!

    If you haven’t already, it is time to seek God with all your heart. Jesus loves you more than you could imagine. He wants to have a relationship with you and redeem you from your sins. Turn to Him and repent while there is still hope! This is forever…God bless!

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  149. Hey, how’s it going?

    I want to pass along some very important news that everyone needs to hear!

    In December of 2017, Donald Trump made history by recognizing Jerusalem as the capital of Israel. Why is this big news? Because by this the Jewish people of Israel are now able to press forward in bringing about the Third Temple prophesied in the Bible.

    Jewish Rabbis have publicly announced that their Messiah will be revealed in the coming years who will be a leader and spiritual guide to all nations, gathering all religions under the worship of one God.

    Biblical prophecy tells us that this Jewish Messiah who will take the stage will be the antichrist “who opposes and exalts himself above all that is called God or that is worshiped, so that he sits as God in the temple of God, showing himself that he is God” (2 Thessalonians 2:4). For a time he will bring about a false peace, but “Therefore when you see the ‘abomination of desolation,’ spoken of by Daniel the prophet, standing in the holy place (Matthew 24:15)…then there will be great tribulation, such as has not been since the beginning of the world until this time, no, nor ever shall be” (Matthew 24:21).

    More importantly, the power that runs the world wants to put a RFID microchip in our body making us total slaves to them. This chip matches perfectly with the Mark of the Beast in the Bible, more specifically in Revelation 13:16-18:

    “He causes all, both small and great, rich and poor, free and slave, to receive a mark on their right hand or on their foreheads, and that no one may buy or sell except one who has the mark or the name of the beast, or the number of his name.

    Here is wisdom. Let him who has understanding calculate the number of the beast, for it is the number of a man: His number is 666.”

    Referring to the last days, this could only be speaking of a cashless society, which we have yet to see, but are heading towards. Otherwise, we could still buy or sell without the mark amongst others if physical money was still currency. This Mark couldn’t be spiritual because the word references two different physical locations. If it was spiritual it would just say in the forehead. RFID microchip implant technology will be the future of a one world cashless society containing digital currency. It will be implanted in the right-hand or the forehead, and we cannot buy or sell without it. Revelation 13:11-18 tells us that a false prophet will arise on the world scene doing miracles before men, deceiving them to receive this Mark. Do not be deceived! We must grow strong in Jesus. AT ALL COSTS, DO NOT TAKE IT!

    “Then a third angel followed them, saying with a loud voice, “If anyone worships the beast and his image, and receives his mark on his forehead or on his hand, he himself shall also drink of the wine of the wrath of God, which is poured out full strength into the cup of His indignation. He shall be tormented with fire and brimstone in the presence of the holy angels and in the presence of the Lamb. And the smoke of their torment ascends forever and ever; and they have no rest day or night, who worship the beast and his image, and whoever receives the mark of his name” (Revelation 14:9-11).

    People have been saying the end is coming for many years, but we needed two key things. One, the Third Temple, and two, the technology for a cashless society to fulfill the prophecy of the Mark of the Beast.

    Visit http://WWW.BIBLEFREEDOM.COM to see proof for these things and why the Bible truly is the word of God!

    If you haven’t already, it is time to seek God with all your heart. Jesus loves you more than you could imagine. He wants to have a relationship with you and redeem you from your sins. Turn to Him and repent while there is still hope! This is forever…God bless!

    “EITHER HUMAN INTELLIGENCE ULTIMATELY OWES ITS ORIGIN TO MINDLESS MATTER OR THERE IS A CREATOR…” – JOHN LENNOX

    We all know God exists. Why? Because without Him, we couldn’t prove anything at all. Do we live our lives as if we cannot know anything? No. So why is God necessary? In order to know anything for certain, you would have to know everything, or have revelation from somebody who does. Who is capable of knowing everything? God. So to know anything, you would have to be God, or know God.

    A worldview without God cannot account for the uniformity and intelligibility of nature. And why is it that we can even reason that God is the best explanation for this if there is no God? We are given reason to know or reject God, but never to know that He does not exist.

    It has been calculated by Roger Penrose that the odds of the initial conditions for the big bang to produce the universe that we see to be a number so big, that we could put a zero on every particle in the universe, and even that would not be enough to use every zero. What are the odds that God created the universe? Odds are no such thing. Who of you would gamble your life on one coin flip?

    Is there evidence that the Bible is the truth? Yes. Did you know that the creation accounts listed in the book of Genesis are not only all correct, but are also in the correct chronological order? That the Bible doesn’t say the Earth was formed in six 24-hour days but rather six long but finite periods of time? That the Bible makes 10 times more creation claims than all major “holy” books combined with no contradictions, while these other books have errors in them? The Bible stood alone by concurring with the big bang saying, “In the beginning God created the heaven and the earth” (Genesis 1:1); and says our universe is expanding, thousands of years before scientists discovered these things. Watch a potential life-changing video on the website listed below with Astronomer(PhD) Hugh Ross explaining all these facts based on published scientific data. He has authored many books, backed even by atheist scientists.

    Jesus came to pay a debt that we could not; to be our legal justifier to reconcile us back to a Holy God; only if we are willing to receive Him: “For the wages of sin is death…” (Romans 6:23).

    God so loved the world that He gave us His only begotten son, so that whoever believes in Him, through faith, shall not perish, but have everlasting life. Jesus says if we wish to enter into life to keep the commands! The two greatest commands are to love God with all your heart, soul, strength, and mind; and your neighbor as yourself. All the law hang on these commands. We must be born of and lead by the Holy Spirit, to be called children of God, to inherit the kingdom. If we are willing to humble ourselves in prayer to Jesus, to confess and forsake our sins, He is willing to give the Holy Spirit to those who keep asking of Him; giving us a new heart, leading us into all truth!

    Jesus came to free us from the bondage of sin. The everlasting fire was prepared for the devil and his angels due to disobedience to God’s law. If we do the same, what makes us any different than the devil? Jesus says unless we repent, we shall perish. For sin is the transgression of the law. We must walk in the Spirit so we may not fulfill the lusts of the flesh, being hatred, fornication, drunkenness and the like. Whoever practices such things will not inherit the kingdom (Galatians 5:16-26). If we sin, we may come before Jesus to ask for forgiveness (1 John 2:1-2). Evil thoughts are not sins, but rather temptations. It is not until these thoughts conceive and give birth by our own desires that they become sin (James 1:12-15). When we sin, we become in the likeness of the devil’s image, for he who sins is of the devil (1 John 3:8); but if we obey Jesus, in the image of God. For without holiness, we shall not see the Lord (Hebrews 12:14).

    The oldest religion in the world is holiness through faith (James 1:27). What religion did Adam and Eve follow before the fall? Jesus, Who became the last Adam, what religion does He follow? Is He not holy? He never told us to follow the rituals and traditions of man but to take up our cross and follow Him (Luke 9:23). There are many false doctrines being taught leading people astray. This is why we need the Holy Spirit for discernment. Unlike religion, holiness cannot be created. It is given to us from above by the baptism of the Spirit. Jesus is more than a religion; He is about having a personal relationship with the Father. Start by reading the Gospel of Matthew, to hear the words of God, to know His character and commandments. Follow and obey Jesus, for He is the way, the truth, and the life!

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    I want to pass along some very important news that everyone needs to hear!

    In December of 2017, Donald Trump made history by recognizing Jerusalem as the capital of Israel. Why is this big news? Because by this the Jewish people of Israel are now able to press forward in bringing about the Third Temple prophesied in the Bible.

    Jewish Rabbis have publicly announced that their Messiah will be revealed in the coming years who will be a leader and spiritual guide to all nations, gathering all religions under the worship of one God.

    Biblical prophecy tells us that this Jewish Messiah who will take the stage will be the antichrist “who opposes and exalts himself above all that is called God or that is worshiped, so that he sits as God in the temple of God, showing himself that he is God” (2 Thessalonians 2:4). For a time he will bring about a false peace, but “Therefore when you see the ‘abomination of desolation,’ spoken of by Daniel the prophet, standing in the holy place (Matthew 24:15)…then there will be great tribulation, such as has not been since the beginning of the world until this time, no, nor ever shall be” (Matthew 24:21).

    More importantly, the power that runs the world wants to put a RFID microchip in our body making us total slaves to them. This chip matches perfectly with the Mark of the Beast in the Bible, more specifically in Revelation 13:16-18:

    “He causes all, both small and great, rich and poor, free and slave, to receive a mark on their right hand or on their foreheads, and that no one may buy or sell except one who has the mark or the name of the beast, or the number of his name.

    Here is wisdom. Let him who has understanding calculate the number of the beast, for it is the number of a man: His number is 666.”

    Referring to the last days, this could only be speaking of a cashless society, which we have yet to see, but are heading towards. Otherwise, we could still buy or sell without the mark amongst others if physical money was still currency. This Mark couldn’t be spiritual because the word references two different physical locations. If it was spiritual it would just say in the forehead. RFID microchip implant technology will be the future of a one world cashless society containing digital currency. It will be implanted in the right-hand or the forehead, and we cannot buy or sell without it. Revelation 13:11-18 tells us that a false prophet will arise on the world scene doing miracles before men, deceiving them to receive this Mark. Do not be deceived! We must grow strong in Jesus. AT ALL COSTS, DO NOT TAKE IT!

    “Then a third angel followed them, saying with a loud voice, “If anyone worships the beast and his image, and receives his mark on his forehead or on his hand, he himself shall also drink of the wine of the wrath of God, which is poured out full strength into the cup of His indignation. He shall be tormented with fire and brimstone in the presence of the holy angels and in the presence of the Lamb. And the smoke of their torment ascends forever and ever; and they have no rest day or night, who worship the beast and his image, and whoever receives the mark of his name” (Revelation 14:9-11).

    People have been saying the end is coming for many years, but we needed two key things. One, the Third Temple, and two, the technology for a cashless society to fulfill the prophecy of the Mark of the Beast.

    Visit http://WWW.BIBLEFREEDOM.COM to see proof for these things and why the Bible truly is the word of God!

    If you haven’t already, it is time to seek God with all your heart. Jesus loves you more than you could imagine. He wants to have a relationship with you and redeem you from your sins. Turn to Him and repent while there is still hope! This is forever…God bless!

    “EITHER HUMAN INTELLIGENCE ULTIMATELY OWES ITS ORIGIN TO MINDLESS MATTER OR THERE IS A CREATOR…” – JOHN LENNOX

    We all know God exists. Why? Because without Him, we couldn’t prove anything at all. Do we live our lives as if we cannot know anything? No. So why is God necessary? In order to know anything for certain, you would have to know everything, or have revelation from somebody who does. Who is capable of knowing everything? God. So to know anything, you would have to be God, or know God.

    A worldview without God cannot account for the uniformity and intelligibility of nature. And why is it that we can even reason that God is the best explanation for this if there is no God? We are given reason to know or reject God, but never to know that He does not exist.

    It has been calculated by Roger Penrose that the odds of the initial conditions for the big bang to produce the universe that we see to be a number so big, that we could put a zero on every particle in the universe, and even that would not be enough to use every zero. What are the odds that God created the universe? Odds are no such thing. Who of you would gamble your life on one coin flip?

    Is there evidence that the Bible is the truth? Yes. Did you know that the creation accounts listed in the book of Genesis are not only all correct, but are also in the correct chronological order? That the Bible doesn’t say the Earth was formed in six 24-hour days but rather six long but finite periods of time? That the Bible makes 10 times more creation claims than all major “holy” books combined with no contradictions, while these other books have errors in them? The Bible stood alone by concurring with the big bang saying, “In the beginning God created the heaven and the earth” (Genesis 1:1); and says our universe is expanding, thousands of years before scientists discovered these things. Watch a potential life-changing video on the website listed below with Astronomer(PhD) Hugh Ross explaining all these facts based on published scientific data. He has authored many books, backed even by atheist scientists.

    Jesus came to pay a debt that we could not; to be our legal justifier to reconcile us back to a Holy God; only if we are willing to receive Him: “For the wages of sin is death…” (Romans 6:23).

    God so loved the world that He gave us His only begotten son, so that whoever believes in Him, through faith, shall not perish, but have everlasting life. Jesus says if we wish to enter into life to keep the commands! The two greatest commands are to love God with all your heart, soul, strength, and mind; and your neighbor as yourself. All the law hang on these commands. We must be born of and lead by the Holy Spirit, to be called children of God, to inherit the kingdom. If we are willing to humble ourselves in prayer to Jesus, to confess and forsake our sins, He is willing to give the Holy Spirit to those who keep asking of Him; giving us a new heart, leading us into all truth!

    Jesus came to free us from the bondage of sin. The everlasting fire was prepared for the devil and his angels due to disobedience to God’s law. If we do the same, what makes us any different than the devil? Jesus says unless we repent, we shall perish. For sin is the transgression of the law. We must walk in the Spirit so we may not fulfill the lusts of the flesh, being hatred, fornication, drunkenness and the like. Whoever practices such things will not inherit the kingdom (Galatians 5:16-26). If we sin, we may come before Jesus to ask for forgiveness (1 John 2:1-2). Evil thoughts are not sins, but rather temptations. It is not until these thoughts conceive and give birth by our own desires that they become sin (James 1:12-15). When we sin, we become in the likeness of the devil’s image, for he who sins is of the devil (1 John 3:8); but if we obey Jesus, in the image of God. For without holiness, we shall not see the Lord (Hebrews 12:14).

    The oldest religion in the world is holiness through faith (James 1:27). What religion did Adam and Eve follow before the fall? Jesus, Who became the last Adam, what religion does He follow? Is He not holy? He never told us to follow the rituals and traditions of man but to take up our cross and follow Him (Luke 9:23). There are many false doctrines being taught leading people astray. This is why we need the Holy Spirit for discernment. Unlike religion, holiness cannot be created. It is given to us from above by the baptism of the Spirit. Jesus is more than a religion; He is about having a personal relationship with the Father. Start by reading the Gospel of Matthew, to hear the words of God, to know His character and commandments. Follow and obey Jesus, for He is the way, the truth, and the life!

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