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CRISPR-Cas9 had its inception in 2012 and a Nobel prize awarded in 2020. CRISPR is a powerful gene-editing technique first discovered in bacteria and adapted for permanent human gene knockout. Alnylam Pharmaceuticals was the first biotech company to gain FDA approval for the gene delivery therapeutic ONPATTRO (patisiran) FDA approved in August 2018. Patisiran was developed in a proprietary lipid formulation to treat transthyretin amyloidosis, also termed ATTR amyloidosis. A...TTR amyloidosis is a rare, fatal disease that causes severe cardio and polyneuropathies and is characterized by the accumulation of amyloid fibrils consisting of misfolded transthyretin (TTR). Patisiran’s siRNA mechanism of action downregulates the production of TTR at a translational level facilitating the degradation of the messenger RNA coding for the misfolded TTR protein. Patisiran is mentioned because although it is a gene therapy, its effects are transient. NTLA-2001 is a new contender in the treatment of ATTR amyloidosis. NTLA-2001 is a lipid formulated CRISPR-Cas9 therapeutic that is currently being tested in a phase I clinical trial to treat ATTR amyloidosis. The researchers found that an infusion of either 0.1 or 0.3 mg/kg of NTLA-2001 in 6 patients, 3 in each group, reduced serum TTR levels by 52% and 87%, respectively. Interestingly, the formulation had minimal side effects and was tolerated exceptionally well. NTLA-2001’s claim to fame is two-fold. First, it is the first time CRISPR has shown clinical utility in a system other than a cell culture plate or an animal model. Second, the effects of CRISPR are not as transient. It is the permanent removal of the affected genome. Although this study concluded at 28 days, their primate data showed TTR knockdown for up to 1 year. https://www.nejm.org/doi/10.1056/NEJMoa2107454 #CRISPR #NTLA-2001 #amyloidosis #liposome #clinicaltrial #geneediting #genetherapy

Bacteria are fascinating little machines. In the past century, we have harnessed the power of bacteria to produce antibiotics, recombinant drugs, and food. We as humans have evolved and lived, sometimes symbiotically, with bacteria, i.e., in the case of intracellular mitochondria and cellular energy production. This same symbiosis is seen with the bacteria that line our guts (microbiota) providing a complex network of physiological functions that help to maintain homeostasis ...within our bodies. This microbiota provides essential metabolites, provides fermentation for non-digestible substrates, influences health, and have preventative cancer functions. I mention these to emphasize the importance of bacteria to human health and industry; however, imagine the possibilities of genetically engineering bacteria to live within our microbiota, with their only role is to produce therapeutic or health-beneficial metabolites on demand. Researchers at Texas A&M University, using a synthetic biology approach, have genetically engineered an on-demand logic circuit with AND and OR gates to modulate the expression of GFP in a genetically engineered GFP producing C. elegans animal model. Feeding the C. elegans E. coli containing either the AND or the OR gated plasmid controls GFP expression. In the AND gated plasmid, the promoters are inducibly controlled using L-Arabinose and anhydrotetracycline to induce the promoter. Meaning that the AND logic gate needs both promoters to be induced in order to facilitate the transcription of interference RNA against GFP production, thus silencing C. elegans GFP gene expression with a >90% efficiency. The OR gated plasmid needs either L-Arabinose or anhydrotetracycline to achieve the same >90% silencing efficiency seen in the AND gate. They were able to expand the logic gated gene expression control to program animal physiology. By substituting the GFP ssRNA coding region with either an unc-22 or sbp-1 ssRNA coding region, they could control C. elegans locomotion through the silencing of unc-2, producing a twitching phenotype, and metabolism by downregulating sbp-1, increasing the worms fat storage. This fundamental bioengineering approach for the on-demand synthesis of biological molecules is the first in many experiments that can potentially engineer bacteria in such a way as to deliver a wide variety of metabolites or therapeutics internally. https://www.nature.com/articles/s41467-021-22894-7 #syntheticbiology #bacterialengineering #therapuetics #siRNA #microbiota

In June, the FDA approved Wegovy for chronic weight management. This subcutaneous injection is the first approved drug for chronic weight management in adults with a high BMI and general obesity since 2014. With 70% of American adults being overweight or obese, there certainly seems to be room for new drug entrants to this growing market. A study recently published in Science magazine looks for answers within the immune system and its ability to regulate adipose tissue within... the skin. Specifically, the study looks at the mechanisms of sebaceous gland sebum production. Sebum is comprised of a mixture of different lipids that protects and makes the skin oily. Interestingly sebum production is mediated by the immune system, more specifically CD4 and CD8 T-cells. This T-cell mediated sebum production is modulated by the holocrine secretion of the cytokine thymic stromal lymphopoietin (TSLP). TSLP, in a physiological sense, is secreted by the skin, activating the T-cell mediated sebum production used for the skin’s antimicrobial effects. However, if you genetically oversecrete or increase TSLP exogenously, then overproduction of sebum occurs, stimulating weight loss. Researchers used a mouse model that over-expressed TSLP in the liver and found that the mice lost weight with no muscle loss reduction and improved metabolic profiles. The brilliance of the research found that while normal T-cell mediated sebum secretion used lipids and lipid debris in the skin, T-cells overstimulated by TSLP increased lipid secretion creating a lipid deficit within the skin. The T-cells mobilize more lipids to compensate for this discrepancy making up for the energy loss spent on sebum production. To mobilize more lipids and increase sebum production, the T-cells start to use circulating blood lipids. What’s fascinating is that the liver senses a drop in freely circulating lipids and starts to use the stored white fat to make up for this decrease, thereby shrinking tummies and thighs. While this all sounds very promising, there are always concerns about potentially detrimental side effects. The researchers pointed out that hypersecretion of sebum on the skin can cause pore blockages and inflammation leading to excessive acne. For some, this may be a temporary and small price to pay for that summer beach body they have been dreaming about for the past decade. https://science.sciencemag.org/content/373/6554/eabd2893 #weightloss #immunesystem #Wegovy #sebumsecrection #cytokinethymicstromallymphopoietin

Birth control is a universal term that encompasses everything from a physical barrier to the chemical inhibition of ovulation. The most common form of contraception, according to the CDC, is female sterilization. Excluding sterilization, the second and third most common forms of birth control are oral contraceptive pills and long-acting reversible contraceptives. The commonality of the latter is that these forms of birth control are hormonally based (excluding ParaGard, the c...opper-based IUD). Hormonally based forms of birth control come with a wide variety of detrimental physiological side effects, including bloating, spotting between periods, migraines, weight gain, mood changes, decreased libido, as well as blood clots that can lead to pulmonary embolisms. Unfortunately, the burden of contraception almost always falls on the shoulders of the woman. Until the advent of a male contraceptive pill, the above-mentioned side effects of hormonally based contraception are an exceptionally heavy crown for women to wear. However, what if is always an enticing question. What if there was a form of birth control that is shown to be 99.9% effective in stopping motile sperm without the need for hormones, injections, implantation, or latex? Shrestha et al. believe they may have discovered such a holy grail. They found an infertile woman who produced IgG antibodies towards unique surface antigens universally present on human sperm. The scientist further optimized the antibodies by engineering them with additional antigen-binding fragments to maximize their agglutination abilities; thus, producing a highly potent multivalent biological birth control. Using 33 g of the multivalent sperm-binding antibody delivered directly into the vagina of a sheep, the researchers were able to test the efficacy and thermal stability of the engineered biological agent against progressively motile spermatozoa, with a >99.9% binding efficiency. Therefore, laying the foundation for a new generation of birth control, one that is devoid of hormonal complications. https://stm.sciencemag.org//scit/13/606/eabd5219.full.pdf #birthcontrol #nonhormonal #IgGagglutination #contraceptive #spermbinding #antibody

Social media is a fantastic development in human communications. However, as with any technology, security should not be an afterthought. Here is a very good list of simple security steps everyone should consider. https://www.networkworld.com//12--tips-for-safe-social-net

Vote BEFORE 5pm ET TODAY for our biotechnology client Treventis Corporation in the Buzz of BIO contest! How to vote: 1. Go here - https://convention.bio.org/buzzofbio-vote/ 2. Complete each field on the right side of the page 3. Select Treventis Corporation under Technologies of Tomorrow 4. Hit submit ... #BIO2019 #biotech See more

Can cars be hacked? Sure they can! Great article by Consumer Reports! https://bit.ly/2EUowhM

Having a secure password is the first step to preventing hackers from accessing your account. Here are the 15 worst passwords from 2018. #webdev #CyberSecurity